21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.
A 21-amino acid peptide produced predominantly within the kidney and intestine, with smaller amounts produced in the myocardium, placenta, and uterus, but the cells of origin are not clear. Endothelin-2 has no unique physiologic functions, as compared with endothelin-1. (N Eng J Med 1995;333(6):356-63)
A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63)
Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.
A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.
A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)
Venoms from SNAKES of the viperid family. They tend to be less toxic than elapid or hydrophid venoms and act mainly on the vascular system, interfering with coagulation and capillary membrane integrity and are highly cytotoxic. They contain large amounts of several enzymes, other factors, and some toxins.
A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
A group of compounds that contain the structure SO2NH2.
Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Drugs used to cause constriction of the blood vessels.
A family of hexahydropyridines.
Poly-2-methylpropenoic acids. Used in the manufacture of methacrylate resins and plastics in the form of pellets and granules, as absorbent for biological materials and as filters; also as biological membranes and as hydrogens. Synonyms: methylacrylate polymer; poly(methylacrylate); acrylic acid methyl ester polymer.
Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight.
Peptides composed of between two and twelve amino acids.
The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.
A thermostable extracellular metalloendopeptidase containing four calcium ions. (Enzyme Nomenclature, 1992)
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
NATIONAL LIBRARY OF MEDICINE service for health professionals and consumers. It links extensive information from the National Institutes of Health and other reviewed sources of information on specific diseases and conditions.
Branch of the common carotid artery which supplies the exterior of the head, the face, and the greater part of the neck.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The largest and uppermost of the paravertebral sympathetic ganglia.
A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.
Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening.
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.
Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.
An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode that ultimately may lead to MYOCARDIAL INFARCTION.
Disease having a short and relatively severe course.

Inhibition of in vitro enteric neuronal development by endothelin-3: mediation by endothelin B receptors. (1/1796)

The terminal colon is aganglionic in mice lacking endothelin-3 or its receptor, endothelin B. To analyze the effects of endothelin-3/endothelin B on the differentiation of enteric neurons, E11-13 mouse gut was dissociated, and positive and negative immunoselection with antibodies to p75(NTR )were used to isolate neural crest- and non-crest-derived cells. mRNA encoding endothelin B was present in both the crest-and non-crest-derived cells, but that encoding preproendothelin-3 was detected only in the non-crest-derived population. The crest- and non-crest-derived cells were exposed in vitro to endothelin-3, IRL 1620 (an endothelin B agonist), and/or BQ 788 (an endothelin B antagonist). Neurons and glia developed only in cultures of crest-derived cells, and did so even when endothelin-3 was absent and BQ 788 was present. Endothelin-3 inhibited neuronal development, an effect that was mimicked by IRL 1620 and blocked by BQ 788. Endothelin-3 failed to stimulate the incorporation of [3H]thymidine or bromodeoxyuridine. Smooth muscle development in non-crest-derived cell cultures was promoted by endothelin-3 and inhibited by BQ 788. In contrast, transcription of laminin alpha1, a smooth muscle-derived promoter of neuronal development, was inhibited by endothelin-3, but promoted by BQ 788. Neurons did not develop in explants of the terminal bowel of E12 ls/ls (endothelin-3-deficient) mice, but could be induced to do so by endothelin-3 if a source of neural precursors was present. We suggest that endothelin-3/endothelin B normally prevents the premature differentiation of crest-derived precursors migrating to and within the fetal bowel, enabling the precursor population to persist long enough to finish colonizing the bowel.  (+info)

Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy. (2/1796)

OBJECTIVE: To determine whether increased plasma concentrations of endothelin-1 (ET-1) and big endothelin (BET) play a role in the regulation of coronary circulation in patients with idiopathic dilated cardiomyopathy (IDCM). SETTING: Tertiary referral centre for cardiac diseases. PATIENTS: Fourteen patients (eight male/six female; mean (SD) age 59 (9) years) with IDCM (ejection fraction 36 (9)%) and five normotensive subjects (two male/three female; age 52 (7) years) serving as controls were studied. METHODS: Functional status was classified according to New York Heart Association (NYHA) class. Endogenous ET-1 and BET plasma concentrations from the aorta and the coronary sinus were determined by radioimmunoassay. Coronary blood flow, using the inert chromatographic argon method, myocardial oxygen consumption, and coronary sinus oxygen content under basal conditions were determined. RESULTS: In the aorta, mean (SD) concentrations of ET-1 (IDCM 0.76 (0.25) v controls 0.31 (0.06) fmol/ml; p = 0.002) and BET (IDCM 3.58 (1.06) v controls 2.11 (0.58) fmol/ml; p = 0.014) were increased in patients with IDCM. Aortic ET-1 concentrations correlated positively with NYHA class (r = 0. 731; p < 0.001), myocardial oxygen consumption (r = 0.749; p < 0. 001), and coronary blood flow (r = 0.645; p = 0.003), but inversely with coronary sinus oxygen content (r = -0.633; p = 0.004), which was significantly decreased in IDCM patients (IDCM 4.68 (1.05) v controls 6.70 (1.06) vol%; p = 0.003). CONCLUSIONS: The coronary circulation in patients with IDCM is exposed to an increased endothelin load. ET-1 concentrations correlate with functional deterioration. A decrease of the coronary sinus content of oxygen suggests a mismatch between coronary blood flow and metabolic demand. Thus, ET-1 might be a marker of a disequilibrium between myocardial oxygen demand and coronary blood flow in IDCM.  (+info)

Endothelin up-regulation and localization following renal ischemia and reperfusion. (3/1796)

BACKGROUND: Endothelin (ET), a potent vasoconstrictor, is known to play a role in ischemic acute renal failure. Although preproET-1 (ppET-1) mRNA is known to be up-regulated following ischemia/reperfusion injury, it has not been determined which component of the injury (ischemia or reperfusion) leads to initial gene up-regulation. Likewise, although ET-1 peptide expression has been localized in the normal kidney, its expression pattern in the ischemic kidney has not been determined. Therefore, the purpose of this study was twofold: (a) to determine whether ischemia alone or ischemia plus reperfusion is required for the up-regulation of ppET-1 mRNA to occur, and (b) to localize ET-1 peptide expression following ischemia in the rat kidney to clarify better the role of ET in the pathophysiology of ischemia-induced acute renal failure. METHODS: Male Lewis rats underwent clamping of the right renal vascular pedicle for either 30 minutes of ischemia (group 1), 60 minutes of ischemia (group 2), 30 minutes of ischemia followed by 30 minutes of reperfusion (group 3), or 60 minutes of ischemia followed by three hours of reperfusion (group 4). The contralateral kidney acted as a control. ppET-1 mRNA up-regulation and ET-1 peptide expression were examined using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Reverse transcription-polymerase chain reaction yielded a control (nonischemic) value of 0.6 +/- 0.2 densitometric units (DU) of ppET-1 mRNA in the kidney. Group 1 levels (30 min of ischemia alone) were 1.8 +/- 0.4 DU, a threefold increase (P < 0.05). Group 2 levels (60 min of ischemia alone) increased almost six times above baseline, 3.5 +/- 0.2 DU (P < 0.01), whereas both group 3 and group 4 (ischemia plus reperfusion) did not experience any further significant increases in mRNA levels (1.9 +/- 0.4 DU and 2.8 +/- 0.6 DU, respectively) beyond levels in group 1 or 2 animals subjected to similar ischemic periods. ET-1 peptide expression in the ischemic kidneys was significantly increased over controls and was clearly localized to the endothelium of the peritubular capillary network of the kidney. CONCLUSIONS: Initial ET-1 gene up-regulation in the kidney occurs secondary to ischemia, but reperfusion most likely contributes to sustaining this up-regulation. The marked increase of ET-1 in the peritubular capillary network suggests that ET-induced vasoconstriction may have a pathophysiological role in ischemic acute tubular necrosis.  (+info)

Nitric oxide limits the eicosanoid-dependent bronchoconstriction and hypotension induced by endothelin-1 in the guinea-pig. (4/1796)

1. This study attempts to investigate if endogenous nitric oxide (NO) can modulate the eicosanoid-releasing properties of intravenously administered endothelin-1 (ET-1) in the pulmonary and circulatory systems in the guinea-pig. 2. The nitric oxide synthase blocker N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 microM; 30 min infusion) potentiated, in an L-arginine sensitive fashion, the release of thromboxane A2 (TxA2) stimulated by ET-1, the selective ET(B) receptor agonist IRL 1620 (Suc-[Glu9,Ala11,15]-ET-1(8-21)) or bradykinin (BK) (5, 50 and 50 nM, respectively, 3 min infusion) in guinea-pig isolated and perfused lungs. 3. In anaesthetized and ventilated guinea-pigs intravenous injection of ET-1 (0.1-1.0 nmol kg(-1)), IRL 1620 (0.2-1.6 nmol kg(-1)), BK (1.0-10.0 nmol kg(-1)) or U 46619 (0.2-5.7 nmol kg(-1)) each induced dose-dependent increases in pulmonary insufflation pressure (PIP). Pretreatment with L-NAME (5 mg kg(-1)) did not change basal PIP, but increased, in L-arginine sensitive manner, the magnitude of the PIP increases (in both amplitude and duration) triggered by each of the peptides (at 0.25, 0.4 and 1.0 nmol kg(-1), respectively), without modifying bronchoconstriction caused by U 46619 (0.57 nmol kg(-1)). 4. The increases in PIP induced by ET-1, IRL 1620 (0.25 and 0.4 nmol kg(-1), respectively) or U 46619 (0.57 nmol kg(-1)) were accompanied by rapid and transient increases of mean arterial blood pressure (MAP). Pretreatment with L-NAME (5 mg kg(-1); i.v. raised basal MAP persistently and, under this condition, subsequent administration of ET-1 or IRL 1620, but not of U-46619, induced hypotensive responses which were prevented by pretreatment with the cyclo-oxygenase inhibitor indomethacin. 5. Thus, endogenous NO appears to modulate ET-1-induced bronchoconstriction and pressor effects in the guinea-pig by limiting the peptide's ability to induce, possibly via ET(B) receptors, the release of TxA2 in the lungs and of vasodilatory prostanoids in the systemic circulation. Furthermore, it would seem that these eicosanoid-dependent actions of ET-1 in the pulmonary system and on systemic arterial resistance in this species are physiologically dissociated.  (+info)

Blockade and reversal of endothelin-induced constriction in pial arteries from human brain. (5/1796)

BACKGROUND AND PURPOSE: Substantial evidence now implicates endothelin (ET) in the pathophysiology of cerebrovascular disorders such as the delayed vasospasm associated with subarachnoid hemorrhage and ischemic stroke. We investigated the ET receptor subtypes mediating vasoconstriction in human pial arteries. METHODS: ET receptors on human pial and intracerebral arteries were visualized with the use of autoradiography, and the subtypes mediating vasoconstriction were identified by means of wire myography. RESULTS: ET-1 was more potent than ET-3 as a vasoconstrictor, indicating an ETA-mediated effect. Similarly, the selective ETB agonist sarafotoxin S6c had no effect on contractile action at concentrations up to 30 nmol/L. The nonpeptide ETA receptor antagonist PD156707 (3 to 30 nmol/L) caused a parallel rightward shift of the ET-1-induced response, yielding a pA2 of 9.2. Consistent with these results, PD156707 (30 nmol/L) fully reversed an established constriction in pial arteries induced by 1 nmol/L ET-1, while the selective ETB receptor antagonist BQ788 (1 micromol/L) had little effect. The calcium channel blocker nimodipine (0.3 to 3 micromol/L) significantly attenuated the maximum response to ET-1 in a concentration-dependent manner without changing potency. In agreement with the functional data, specific binding of [125I]PD151242 to ETA receptors was localized to the smooth muscle layer of pial and intracerebral blood vessels. In contrast, little or no [125I]BQ3020 binding to ETB receptors was detected. CONCLUSIONS: These data indicate an important role for ETA receptors in ET-1-induced constriction of human pial arteries and suggest that ETA receptor antagonists may provide additional dilatory benefit in cerebrovascular disorders associated with raised ET levels.  (+info)

Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. (6/1796)

BACKGROUND: The participation of endothelin-1 (ET-1) in the control of vascular tone in humans has been questioned, on the basis of the finding of subthreshold immunoreactive (ir) ET-1 plasma levels. However, because most ET-1 is secreted abluminally, it might attain a higher concentration in the tunica media than in plasma. Furthermore, evidence indicates that vascular smooth muscle cells (VSMCs) can synthesize ET-1 on stimulation in vitro. We therefore looked for irET-1 in the different layers of the wall of human arteries, including renal, gastric, and internal thoracic artery wall, obtained ex vivo from consenting patients with coronary artery disease and/or high blood pressure undergoing surgery, as well as from young organ donors. METHODS AND RESULTS: We performed immunohistochemistry with specific anti-ET-1 and anti-vWF antibodies followed by detection with an avidin-biotin complex ultrasensitive kit. The presence of preproET-1 and human endothelin-converting enzyme-1 (hECE-1) mRNA was also investigated by reverse transcription-polymerase chain reaction in homogenates of vessel wall, including preparations deprived of both endothelium and adventitia, and in isolated VSMCs. We detected irET-1 in the endothelium of all arteries and in the tunica media of internal thoracic artery from most patients with coronary artery disease. PreproET-1 and hECE-1 mRNA was also detected in VSMCs isolated from these vessels. irET-1 and irvWF staining in endothelium and tunica media was measured by use of microscope-coupled computer-assisted technology. Significant correlations between the amount of irET-1 in the tunica media and mean blood pressure (P<0.05), total serum cholesterol (P<0.05), and number of atherosclerotic sites (P<0.001) were found. Thus, in organ donors, irET-1 was detectable almost exclusively in endothelial cells, whereas in patients with coronary artery disease and/or arterial hypertension, sizable amounts of irET-1 were detectable in the tunica media of different types of arteries. In addition, VSMCs isolated from these vessels coexpressed the preproET-1 and hECE-1 genes. CONCLUSIONS: Collectively, these findings are consistent with the contention that endothelial damage occurs in most patients with atherosclerosis and/or hypertension and that ET-1 is synthesized in VSMCs of these patients.  (+info)

Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. (7/1796)

BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of +info)

Maintenance of blood pressure in normotensive dogs by endothelin. (8/1796)

The role of endothelin (ET)-1 in blood pressure homeostasis and the interaction with the renin-angiotensin system (RAS) was investigated in normotensive conscious dogs. ETA receptors were blocked by LU-135252 (1-30 mg/kg); trandolapril (2 mg/kg) or losartan (10 mg/kg) was used to inhibit the RAS. LU-135252 in oral doses of 3-30 mg/kg significantly reduced mean arterial pressure (MAP) by approximately 10 mmHg maximally, whereas trandolapril or losartan were without any effect. MAP reduction was more pronounced when LU-135252 was combined with either losartan (-15.5 +/- 3.2 mmHg; 2 h postadministration; P < 0.05) or trandolapril (-30.9 +/- 3.6 mmHg; P < 0.05). When endogenous nitric oxide (NO) generation was blocked but NO concomitantly infused, this synergistic effect on MAP was prevented. The data show that ET-1 contributes to the maintenance of blood pressure via ETA receptors. Furthermore, ET-1 and ANG II play a prominent role in the control of blood pressure by opposing the effects of NO. The pronounced blood pressure fall after combined blockade of ETA receptors and the RAS may be mediated by an enhanced release of NO.  (+info)

TY - JOUR. T1 - Plasma endothelin concentrations in humans with end-stage heart failure and after heart transplantation. AU - Lerman, Amir. AU - Kubo, Spencer H.. AU - Tschumperlin, Linda K.. AU - Burnett, John C.. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 1992/10. Y1 - 1992/10. N2 - Objectives and Background. Endothelin is an endothelium-derived vasoconstrictor peptide that increases systemic and renal vascular resistance at pathophysiologic concentrations. Recent studies have demonstrated its presence in the circulation and its elevation in animals with congestive heart failure, suggesting that endothelin may contribute to the vasoconstrictive state of heart failure. The current study was designed with two objectives: 1) to demonstrate the elevation or circulating endothelin in patients with heart failure, and 2) to determine the short- and long-term response of endothelin levels after heart transplantation. Methods. Plasma endothelin concentrations were measured ...
TY - JOUR. T1 - Release of endothelin during reperfusion of ischemic myocardium. AU - Maulik, N.. AU - Subramanian, R.. AU - Liu, X.. AU - Das, D. K.. PY - 1992. Y1 - 1992. N2 - Endothelin, the most potent endothelium-derived vasoconstrictor, was found to be released from the isolated ischemic rat heart after a prolonged period of reperfusion. No endothelin release was observed up to 1 hour of reperfusion following 30 minutes of global ischemic arrest. Although most of the endothelin release occurred as a burst after 1 hour of reperfusion, the endothelin release increased progressively at a slower rate up to 2 hours of reperfusion. The calcium slow channel blocker, nifedipine, and the phospholipase inhibitor, mepacrine, but not the free radical scavengers, superoxide dismutase (SOD) and catalase, prevented the endothelin release from the heart. Unlike endothelin release that did not occur until after 1 hour of reperfusion, lipid peroxidation assessed by thiobarbituric acid reactive product ...
TY - JOUR. T1 - Circulating and Tissue Endothelin Immunoreactivity in Advanced Atherosclerosis. AU - Lerman, Amir. AU - Edwards, Brooks S.. AU - Hallett, John W.. AU - Heublein, Denise M.. AU - Sandberg, Sharon M.. AU - Burnett, John C.. PY - 1991/10/3. Y1 - 1991/10/3. N2 - Background. Atherosclerosis is characterized by endothelial injury and the proliferation of arterial smooth-muscle cells. The latter may be a result of the release of growth factors from the vessel wall; such growth factors may include an endothelium-derived vasoconstrictor peptide with mitogenic properties. We tested the hypothesis that plasma endothelin concentrations are elevated in persons with symptomatic atherosclerosis, independently of age. Methods. We measured plasma endothelin levels in 100 normal subjects and in 40 patients with atherosclerosis predominantly of the following types: aortic and peripheral vascular disease (14 patients), renovascular disease (9 patients), coronary artery disease (9 patients), and ...
To the best of our knowledge, this is the first study to demonstrate differences between aortic and coronary sinus endothelin concentrations in IDCM and to link ET-1 and BET plasma concentrations to the coronary circulation in regard to myocardial oxygen demand, coronary sinus oxygen content, and coronary blood flow at basal conditions in patients with IDCM.. As stated by other investigators,4 7 8 we found that in patients with IDCM with increasing NYHA class the plasma concentrations of immunoreactive ET-1/BET in arterial samples were increased. This was correlated with an increase in internal left ventricular dimensions and a decreased ejection fraction. An increment of ET-1/BET concentrations in venous samples of patients with CHF was described by Pacheret al and Pousset et al to be of prognostic importance, independent from haemodynamic data in patients with CHF.7 8 Therefore, our results are in accordance with the hypothesis that, with progressive heart failure, the endothelin system is ...
TY - JOUR. T1 - Heparin regulates endothelin production through endothelium-derived nitric oxide in human endothelial cells. AU - Yokokawa, Koji. AU - Tahara, Hideki. AU - Kohno, Masakazu. AU - Mandal, Anil K.. AU - Yanagisawa, Masashi. AU - Takeda, Tadanao. PY - 1993. Y1 - 1993. N2 - Heparin shows blood pressure lowering effect in hypertensive patients and animal models. The present study examined the effect of heparin on vasoconstrictor endothelin-1 (ET-1) production in cultured human umbilical vein endothelial cells (ECs) to elucidate the mechanism of antihypertensive effect of heparin. Heparin suppressed both basal and thrombin-stimulated ET-1 mRNA expression paralleled with a decrease in ET-1 peptide release in a dose-dependent manner. Heparin concomitantly enhanced nitric oxide (NO) formation measured by NO2/NO3 levels and cGMP production in ECs. These enhancements were more marked when ECs were stimulated by thrombin. However, these heparins effects were blunted in the presence of ...
Peptides , Cyclic Peptides , Disulfide Cyclized Peptides , Big Endothelin-1 (1-38), human; Big Endothelin-1 (1-38) is precursor of endothelin 1. Big endothelin-1 is cleaved to yield endothelin-1 via the activity of an endothelin-converting enzyme (ECE). Big Endothelin-1 can be hydrolyzed by chymase to generate endothelin 1 (1-21) in vitro. Endothelins are endothelium-derived vasoconstrictor peptides.; CSCSSLMDKECVYFCHLDIIWVNTPEHVVPYGLGSPRS (Disulfide bridge: 1-15 and 3-11); H-Cys-Ser-Cys-Ser-Ser-Leu-Met-Asp-Lys-Glu-Cys-Val-Tyr-Phe-Cys-His-Leu-Asp-Ile-Ile-Trp-Val-Asn-Thr-Pro-Glu-His-Val-Val-Pro-Tyr-Gly-Leu-Gly-Ser-Pro-Arg-Ser-OH (Disulfide bridge: 1-15 and 3-11)
Endothelins are potent endothelium-derived vasoconstrictors 1. The endothelin system has been reported to be activated in various types of experimental or clinical pulmonary hypertension 1. However, whether endogenous endothelins play a role in the control of systemic and pulmonary vascular tone in vivo remains uncertain. Endothelin receptor antagonists have been shown to increase forearm blood flow in humans 2, 3, to reduce brachial artery pressure in patients with essential hypertension 4 and to decrease pulmonary artery pressure in patients with primary pulmonary hypertension 5, 6. However, some investigators have been unable to demonstrate pulmonary or systemic vascular effects of these compounds in vivo 7-17. The failure to show a vasoconstrictor effect of endogenous endothelins appears related, at least in part, to the release of nitric oxide (NO) by the endothelium, which either counteracts the effect and/or inhibits the synthesis of endothelins 16-19.. Endothelins have been hypothesised ...
TY - JOUR. T1 - Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. AU - Nelson, J. B.. AU - Hedican, S. P.. AU - George, D. J.. AU - Reddi, A Hari. AU - Piantadosi, S.. AU - Eisenberger, M. A.. AU - Simons, J. W.. PY - 1995. Y1 - 1995. N2 - Prostate cancer is the second most common cause of death from cancer in U.S. men, and advanced, hormone-refractory disease is characterized by painful osteoblastic bone metastases. Endothelin-1, more commonly known as a potent vasoconstrictor, is a normal ejaculate protein that also stimulates osteoblasts. We show here that plasma immunoreactive endothelin concentrations are significantly elevated in men with metastatic prostate cancer and that every human prostate cancer cell line tested produces endothelin-1 messenger RNA and secretes immunoreactive endothelin. Exogenous endothelin-1 is a prostate cancer mitogen in vitro and increases alkaline phosphatase activity in new bone formation, indicating that ...
Endothelins are potent peptide vasoconstrictors which were discovered two decades back. Their role in cardiovascular diseases, cancer, glaucoma, diabetes mellitus and many other diseases have been studied. Inspite of a lot of research many questions regarding their pathophysiological roles still remain unanswered. Though many endothelin receptor antagonists showed promising results in animal studies they failed to show significant improvement in clinical practice. The limitations of receptor antagonists lead to the research on synthesis inhibitors and their combinations with ACE inhibitors. This article summarizes the path of endothelins from their discovery to their current status and future prospects.. ...
The mitogenic activity of endothelin and its ability to stimulate PtdIns(4,5)P2 and phosphatidylcholine turnover in Rat-1 fibroblasts was studied. Stimulated incorporation of [3H]thymidine occurred in the absence of any other added growth factors. The endothelins stimulated rapid generation of both Ins(1,4,5)P3 and choline. Endothelin-1 and endothelin-2 were equipotent in stimulating both responses, but endothelin-3 was less potent. Endothelin-1-stimulated Ins(1,4,5)P3 generation reached a maximum at 5 s and then declined; however, the response was long-lived, with a 4.5-fold elevation over basal still observed after 15 min. Endothelin-stimulated choline generation was observed with no increase in choline phosphate; indeed, the apparent level of this metabolite fell after 30 min of stimulation, presumably due to the observed stimulation of phosphatidylcholine synthesis. The endothelin-stimulated increase in choline generation was abolished in cells where protein kinase C was down-regulated. ...
TY - JOUR. T1 - Cerebral microvascular responses to endothelins. T2 - The role of ET(A) receptors. AU - Sagher, O.. AU - Jin, Y.. AU - Thai, Quoc-Anh. AU - Fergus, A.. AU - Kassell, N. F.. AU - Lee, K. S.. PY - 1994. Y1 - 1994. N2 - The regulatory role of endothelins in cerebral microvessels was investigated in a recently developed model system which allows the study of small cerebral vessels in their normal microenvironment. Using brain slices of the rat neocortex, it was shown that the isopeptide endothelin-3 (ET-3) had no effect on cerebral microvessels, while the isopeptide endothelin-1 (ET-1) produced a potent, dose-dependent vasoconstriction. When a recently developed antagonist of ET(A) receptors (Cyclo-[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]; ETant) was administered prior to treatment with ET-1, the vasoconstrictor response to ET-l was inhibited in a dose-dependent manner. When ETant was administered after the establishment of a constriction by ET-l, the constrictor response to ET-1 was ...
Endothelins are among the most potent vasoconstrictor proteins known. Overexpression of endothelins contributes to hypertension and heart disease. Three isoforms are known, each containing 21 amino acids: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). All three isoforms are encoded by a 38-amino-acid precursor known as big endothelin. Endothelins are expressed in many tissues, including lung, kidney, brain, pituitary, and placenta. ...
TY - JOUR. T1 - Expression of a recombinant preproendothelin-1 gene in arteries stimulates vascular contractility. AU - Schott, Eckart. AU - Tostes, Rita C A. AU - San, Hong. AU - Paul, Martin. AU - Clinton Webb, R.. AU - Nabel, Elizabeth G.. PY - 1997/5/17. Y1 - 1997/5/17. N2 - Endothelin (ET)-l is a potent vasoconstrictor peptide that is elevated in cardiovascular diseases. However, the biological function of ET-1 gene expression within arteries in vivo has not been determined. The effects of ET-1 gene expression were investigated using gene-transfer methods on porcine vascular cells in vitro and porcine arteries in vivo. Transfection of vascular cells with a vector encoding for human preproendothelin-1 cDNA1 (pVR-ppET) resulted in significant increases in active ET-1 levels in culture supernatant compared with nontransfected cells (P , 0.05). This supernatant contracted rat aortic strips at concentrations 10-fold lower than synthetic ET-1 protein,. which was inhibited by the ET-A receptor ...
Overactive endothelins can contribute to heart, lung, kidney disorders, and more. Learn the endothelin roles & factors that increase/decrease them.
WG Haynes; Endothelins as Regulators of Vascular Tone in Man. Clin Sci (Lond) 1 December 1994; 87 (s31): 33P-34P. doi: https://doi.org/10.1042/cs045033Pc_pt2. Download citation file:. ...
Severn Biotech, Limited : Endothelins and Related Peptides - Electrophoresis Products PBS & Saline Solutions Hybridisation Reagents Biological Buffers & SDS Sodium Azide Solutions General Bio-chemical Products Fingerprinting Chemical Product Forensic Dyes & Chemicals HPLC Laboratory Solvents DNA / RNA Extraction Specialist Pure Water Products Protein Linker Conjugates Peptide Synthesis Reagents Alcohol Sprays Hand Sanitiser Products Customised Services Comet Assay Products Protein Antibody Reagents Scientific Plastics Catalogue Peptides Affinity Purification Materials Cytology Screening Antibodies Specials severn, biotech
The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety…
Sigma-Aldrich offers Sigma-E6139, Big Endothelin 2 human for your research needs. Find product specific information including CAS, MSDS, protocols and references.
This patent search tool allows you not only to search the PCT database of about 2 million International Applications but also the worldwide patent collections. This search facility features: flexible search syntax; automatic word stemming and relevance ranking; as well as graphical results.
Endothelial cells produce the 21-amino acid peptide endothelin, which is formed from its precursor, big endothelin, via the activity of converting enzyme. The basal production of the peptide is stimulated by epinephrine, angiotensin II, arginine vasopressin, transforming growth factor beta, thrombin …
This gene encodes a member of the endothelin protein family of secretory vasoconstrictive peptides. The preproprotein is processed to a short mature form which functions as a ligand for the endothelin receptors that initiate intracellular signaling events. This gene product is involved in a wide range of biological processes, such as hypertension and ovulation. Altered expression of this gene is implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014 ...
Out of the study population, 57 (37.01%), 40 (25.97%), and 57 (37.01%) participants were HIV positive on treatment, HIV positive not on treatment and HIV negative respectively (Figure 1). Most of the variables presented show no significant difference between the three study groups. However, endothelin and NO levels were significantly different between the study groups(P,0.0001) in table 3. Interaction of blood pressure and Body Mass Index across the HIV status groups are shown in table 4. There was no significant difference in SBP among the different groups. There was a significant difference in DBP and PP between the study groups (p,0.0001). Table 5 shows associated factors attributed to the presence of arterial hypertension in few participants (n=54). There was no significant variation of mean values of nitric oxide or endothelin among hypertensive and non-hypertensive patients. However, there was a significant association in other variables presented. Endothelin levels were higher in ...
Question - Acne since a long time, relieved for a short time with Iret. Is this medicine ineffective for long period of time?. Ask a Doctor about uses, dosages and side-effects of Iret capsules, Ask a Dermatologist
Des produits Purs et Bruts, à lécart de la cosmétologie classique, aliant qualité dextraction de ses composants et concentration extrême dactifs.
Des produits Purs et Bruts, à lécart de la cosmétologie classique, aliant qualité dextraction de ses composants et concentration extrême dactifs.
Des produits Purs et Bruts, à lécart de la cosmétologie classique, aliant qualité dextraction de ses composants et concentration extrême dactifs.
We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, ...
This is the first study to investigate the effects of tezosentan, a non-selective endothelin receptor antagonist, in LPS challenged rats with cirrhosis. LPS was administered intravenously, followed by intravenous administration of tezosentan or placebo one hour later. Thus the study design mimics the occurrence of severe endotoxaemia by intravenous administration of a Gram negative bacterial product. In this study, normal rats were not investigated as we observed that 1 mg/kg LPS intravenously had only minor effects on serum transaminase activities and had no lethal effects (unpublished results, Moreau and Lebrec, 2001). Similar findings have been previously observed.6,7. In this series of rats with cirrhosis, LPS administration induced a significant decrease in arterial pressure and an increase in plasma endothelin levels associated with elevated serum transaminase activities and high mortality indicating endotoxin induced liver injury. These results were similar to those previously observed ...
TY - JOUR. T1 - Central obesity and hypertension: the role of plasma endothelin. Am J Hypertens. AU - Licata, Giuseppe. AU - Corrao, Salvatore. AU - Scaglione, Rosario. AU - Parrinello, Gaspare. AU - Licata, Anna. AU - Pinto, Antonio. AU - Parrinello, Gaspare. PY - 1996. Y1 - 1996. N2 - Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normotensives and in 57 ...
TY - JOUR. T1 - Endothelin antagonism reduces circulating galectin-3 in patients with proteinuric chronic kidney disease. AU - Farrah, Tariq E. AU - Anand, Atul. AU - Miller-Hodges, Eve. AU - Mills, Nicholas L. AU - Webb, David J. AU - Dhaun, Neeraj. PY - 2018/1. Y1 - 2018/1. KW - Endothelin Receptor Antagonists. KW - Endothelins. KW - Galectin 3. KW - Humans. KW - Proteinuria. KW - Renal Insufficiency, Chronic. U2 - 10.1016/j.kint.2017.10.009. DO - 10.1016/j.kint.2017.10.009. M3 - Letter. C2 - 29291821. VL - 93. SP - 270. JO - Kidney International. JF - Kidney International. SN - 0085-2538. IS - 1. ER - ...
Stroke-prone spontaneously hypertensive rats receiving a high salt diet were orally treated by the calcium antagonist lacidipine, at a dose which did not reduce systolic blood pressure. We observed that lacidipine inhibited the salt-induced cardiac hypertrophy and the concomitant increase of mRNA transcripts for preproendothelin-1 in ventricles. These data show that elevated blood pressure cannot necessarily account for cardiac hypertrophy and indicate that the therapeutic action of lacidipine is not only related to its haemodynamic properties, but also to the inhibition of the gene expression of growth factors such as endothelin. ...
back to overview Endothelins are vasoconstricting peptides produced by vascular endothelial cells. The endothelin family consists of three members, endothelin-1; endothelin-2; and endothelin-3.. back to overview ...
cDNA cloning and chromosomal assignment of the endothelin 2 gene: vasoactive intestinal contractor peptide is rat endothelin 2.: Four members of the endothelin
Whether the adventitia component of blood vessels directly participates in the regulation of vascular tone remains to be demonstrated. We have recently developed a human tissue-engineered blood vessel comprising the three tunicae of a native blood vessel using the self-assembly approach. To investigate the role of the adventitia in the modulation of vascular tone, this tissue-engineering method was used to produce three vascular constructs from cells explanted and proliferated from donor vessel tunicae 1) an adventitia + a media, or only 2) an adventitia, or 3) a media. The vasoconstriction responses of these 3 constructs to endothelin, the most potent vasopressor known up-to-date, as well as to nonselective and selective agonists and antagonists, were compared. The adventitia contracted to endothelin-1, -2, whereas the media and the media+adventitia contracted to all three endothelins. Endothelin-induced contraction of the adventitia was dependent on ETA receptors, whereas that of the media and ...
We investigated the effect of systemic hypoxia (Krebs-Henseleit solution gassed with 5% CO2/95% N2) on an isolated, perfused rat lung. Hypoxia resulted in a slowly developing sustained increase in pulmonary perfusion pressure (PPP) accompanied by an increase in lung weight (LW). The endothelin (ET) receptor antagonists BQ123 (3 and 10 μM), BQ788 (3 μM) and bosentan (1.5 and 5 μM) all attenuated the hypoxia-induced increases in LW and PPP. In addition, phosphoramidon (1 μM), an ET-converting enzyme inhibitor, also significantly attenuated the hypoxia-induced increases in PPP and LW. The use of two agents that alter peptide secretion, phalloidin (10 and 50 nM) and colchicine (100 nM), and the peptide synthesis inhibitor cycloheximide (5 μM) all significantly attenuated the hypoxia-induced increases in PPP and LW. The increase in PPP and LW after the onset of hypoxia was accompanied by an increase in perfusate levels of ET-1 compared with normoxic time-matched controls. The results show that ...
The current understanding of the mechanisms of action of insulin and cellular interactions of insulin with endothelin supports an expectation for both vascular and nonvascular effects of endothelin antagonism on insulin action. The discovery of endothelin as a vasoconstrictor agent produced by the endothelium prompted initial explorations of its role as a modulator of vascular function (39). The net tissue actions of insulin in skeletal muscle depend in part on the capacity of the vasculature to vasodilate in response to insulin (12,40,41), with this vasodilation actively redistributing blood flow in support of the increased metabolism (13). This vascular action of insulin is impaired in states of insulin resistance (9,42,43), and we and others have previously shown that increased endogenous endothelin contributes to vascular dysfunction in obesity and diabetes (7,8). Based on these observations, we had an a priori expectation that endothelin antagonism would improve insulin-stimulated ...
We previously reported that sodium excretion is significantly correlated to the excretion of nitrate/nitrite, cGMP, and endothelin in normotensive young adults....
Characterization of canine pericardial fluid endothelin-1 levels.: Recently, extremely high concentrations of endothelin-1 (ET-1) were detected in the pericardi
Looking for something similar?IRL - Feb 2014March/April IRL 2015May 2016 IRL - making goals and making it happenIRL Feb 2015 more
TY - JOUR. T1 - Increased immunoreactive endothelin-1 in human transplant coronary artery disease. AU - Ravalli, Stefano. AU - Szabolcs, Matthias. AU - Albala, Arline. AU - Michler, Robert E.. AU - Cannon, Paul J.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - Background: The pathogenesis of transplant coronary artery disease (TCAD) is unknown, but it is thought to derive from an interaction between immune and nonimmune factors, leading to smooth muscle cell proliferation and accumulation in the expanded neointima. Endothelin-1 (ET-1), a potent vasoconstrictor with mitogenic properties for vascular smooth muscle cells, has recently been demonstrated in native vessel atherosclerosis. The present study used immunohistochemistry to investigate the role of ET-1 in TCAD. Methods and Results: ET-1 immunoreactivity and cellular localization were assessed in human coronary arteries with TCAD (n=13) and in normal coronary arteries (n=10) with single- and double-label immunohistochemistry. The intensity of ...
The present study demonstrates that long-term oral l-arginine supplementation for 6 months in humans with nonobstructive coronary artery disease improves coronary small-vessel endothelial function in response to acetylcholine in association with a significant improvement in their symptoms. The group that received l-arginine demonstrated an improvement in endothelial function at the level of both the epicardial and small coronary vessels. This improvement in coronary endothelial function was associated with a decrease in plasma endothelin concentrations. This study proposes a role for l-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.. The endothelium is an important modulator of coronary vascular tone through the release of endothelium-derived relaxing factors such as NO and endothelium-derived vasoconstrictors such as endothelin.2 Early coronary atherosclerosis is associated with coronary endothelial dysfunction, ...
It is established that peptidemimetic drugs, such as renin inhibitors, somatostatin analogs, and endothelin antagonists, are often efficiently excreted into the bile in an unchanged form, resulting in their low bioavailability (Bertrams et al., 1991a,b;Greenfield et al., 1989; Nakamura et al., 1996). However, the present study shows that both the CLtotal andCLbile, p differ between various endothelin antagonist. Compound A has a 4-fold lowerCLtotal than that of BQ-485 (Table 1).CLbile, p also differs between each compound, with an 8-fold difference between compound A and BQ-485 (Table 1). The inhibition constant of compound A for binding to ETA is in the nanomolar range, as in the case of BQ-485 and BQ-123 (22, 3.4, and 13 nM for BQ-123, BQ-485, and compound A, respectively) (Fukami et al., 1996; Itoh et al., 1993; Moreland et al., 1994). This means that it is possible to construct a small peptide, like compound A, that exhibits relatively lower hepatic extraction but still has potent antagonist ...
Background & Aims: Endothelin_1 secreted by endothelial cells has been identified as the strongest vascular constrictor. The aim of the present study was to investigate the role of concurrent training on plasma concentration of endothelin_1 and its relationship with blood pressure of old women. Methods: A total of 20 menopause women (Mean age: 67.47±5.92 years, mean body length: 152.92±7.52cm, mean weight: 65.83±11.83 kg, mean BMI 28.47±4.98 kg/m2 , fat percentage: 18.61±3.57, and WHR: 0.929±0.045) were selected purposefully and randomly assigned into the two groups of ten people. The experimental group did eight weeks of concurrent training in the form of three days per week each day two sessions resistance training with the intensity of 40 to 65% of one maximum repetition and with overload of 5% after each 6 sessions and aerobic training with 60 to 70% of maximum heart rate. Before and after eight weeks of exercise, the resting level of endothelin_1 and systolic and diastolic blood pressure were
TY - JOUR. T1 - Weight loss reduces plasma endothelin-1 concentration in obese men. AU - Maeda, Seiji. AU - Jesmin, Subrina. AU - Iemitsu, Motoyuki. AU - Otsuki, Takeshi. AU - Matsuo, Tomoaki. AU - Ohkawara, Kazunori. AU - Nakata, Yoshio. AU - Tanaka, Kiyoji. AU - Goto, Katsutoshi. AU - Miyauchi, Takashi. PY - 2006/6. Y1 - 2006/6. N2 - Obesity is associated with endothelial dysfunction that may contribute to the development of diabetes, hypertension, and atherosclerosis. Endothelin-1 (ET-1), which is produced mostly by vascular endothelial cells, has potent vasoconstrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and the progression of atherosclerosis, suggesting that ET-1 may be important in endothelial dysfunction. We studied whether diet-induced weight loss (i.e., lifestyle modification) affects plasma ET-1 concentration in obese individuals. We measured plasma ET-1 concentration in seven obese men (age: 48 ...
Endothelins (ET-1, 2, and 3) are considered to be very powerful vasoconstrictive substances. In humans, endothelins mediate their actions via two…
The pathophysiology of renal dysfunction is much more complex than simply reduced cardiac output. Vascular factors such as nitric oxide, prostaglandin, natriuretic peptides, and endothelin may mediate renal perfusion independently of cardiac hemodynamics.. The heart, kidneys, renin-angiotensin system, sympathetic nervous system, immune system, and endothelium often interact through intricate feedback loops. An imbalance in this complex system will often cause deterioration in both cardiac and renal function.. If cardiac output and mean arterial pressure fall, so does renal blood flow, activating the renin-angiotensin system, reducing nitric oxide in the endothelium, activating the sympathetic nervous system, and inducing inflammatory mediators, all of which, in a vicious circle, cause structural and functional damage to the kidneys and heart. Recently, researchers have been focusing on the role of inflammatory markers as links between cardiovascular and kidney disease.. For example, C-reactive ...
FUNCTION: This gene encodes a member of the endothelin family of peptides. The encoded preproprotein undergoes proteolytic processing to generate a peptide before secretion by the vascular endothelial cells. The mature peptide has various biological activities such as vasoconstriction, cell proliferation, stimulation of hormone release and modulation of central nervous activity. Mice lacking the encoded protein exhibit neonatal lethality accompanied with numerous craniofacial and cardiovascular defects due to disruption in cranial and cardiac neural crest cell patterning during early embryogenesis. [provided by RefSeq, Feb 2016 ...
Information on the #B7EDCF html color code with its RGB and HSL make up, lighter and darker colors, analogous colors, and trinary colors.
Thought I would add a positive post to this board as I know how it can get sometimes.Cant really say much about this irl as a lot of people think it
Recent gene targeting studies have revealed unexpected roles for endothelins in the development of neural crest-derived tissues. Endothelin converting enzyme-1 (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to endothelin-1(ET-1) in vitro. However, the importance of ECE-1 cleavage in the multiple endothelin pathways in vivo is unknown. Here we generated a targeted null mutation in the mouse ECE-1 gene. ECE-1−/− term embryos exhibited craniofacial and cardiac abnormalities virtually identical to the defects seen in ET-1 and endothelin A receptor (ETA)-deficient embryos. Epidermal melanocytes as well as enteric neurons of the distal gut were also absent in ECE-1−/− embryos, reproducing the developmental phenotype seen in ET-3−/− and endothelin B receptor (ETB)−/− mice. Surprisingly, large amounts of mature ET-1 peptide are found in ECE-1−/− embryos, indicating that non-ECE-1 protease(s) can activate ET-1 at certain sites. However, these enzymes cannot produce ...
Endothelin 1 may have a role in the development of acute airway narrowing in asthma. Blockade of the endothelin system may thereby protect against airway narrowing. Two receptors exist for endothelin 1, Endothelin A & B. Both can be blocked by Bosentan, and the A receptor by ambrisentan. Both medications are currently in use for the treatment of pulmonary arterial hypertension. The investigators will endeavour to examine the potential role of endothelin 1 in the development of airway narrowing in asthma through blockade of the endothelin receptors A&B through the use of bosentan and ambrisentan ...
TY - JOUR. T1 - Development of a new endotoxin sensor with intermittent injection of limulus reagent for continuous monitoring of dialysate fluid. AU - Aoyagi, S.. AU - Yoshimi, Y.. AU - Sakai, K.. AU - Aketagawa, J.. AU - Tanaka, S.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - This report describes a method of continuously, stably, and inexpensively measuring endotoxin (ET) concentrations in dialysate fluid using an ET sensor with intermittent injection of limulus reagent. An ET solution simulating dialysate fluid was sampled in a single tube at a flow rate of 260 μl/min and mixed with 30 μl of limulus reagent intermittently injected into the tube. The absorbance of the solution was measured after the limulus reaction at 313 or 318° K at 26 min. A good linear relationship (r = 0.98) between peak area of absorbance and ET concentration at ET concentrations ranging from 0 to 0.12 endotoxin unit (EU)/ml was obtained, using a spectrophotometer with a cell volume of 8 μl. The baseline rose after the ...
Introduction. Endothelin-1 (ET-1), together with its cognate receptors endothelin receptor subtype A (ET-RA) and endothelin receptor subtype B (ET-RB), is known to be one of the many mediators that play a role in angiogenesis.1 For example, it has been shown that ET-1, acting via ET-RB and in concert with vascular endothelial growth factor (VEGF), promotes proliferation, migration and invasion of umbilical vein endothelial cells (HUVECs).2 The ET axis has also been found to be over-expressed by cancer cells and there is evidence that it is involved, in association with VEGF and other factors, in tumour angiogenesis.3 For example, in ovarian cancer, ET-1 stimulates early neovascularisation (proliferation and migration of endothelial cells) via ET-RB receptors.4 The ET system also plays a less direct role in angiogenesis by, for example, breaking down the extracellular matrix.3,5 Studies have linked increased tumour vascularity to ET-1 in brain tumours, ovarian and colorectal cancer,4,6,7 and in a ...
Introduction. Endothelin-1 (ET-1), together with its cognate receptors endothelin receptor subtype A (ET-RA) and endothelin receptor subtype B (ET-RB), is known to be one of the many mediators that play a role in angiogenesis.1 For example, it has been shown that ET-1, acting via ET-RB and in concert with vascular endothelial growth factor (VEGF), promotes proliferation, migration and invasion of umbilical vein endothelial cells (HUVECs).2 The ET axis has also been found to be over-expressed by cancer cells and there is evidence that it is involved, in association with VEGF and other factors, in tumour angiogenesis.3 For example, in ovarian cancer, ET-1 stimulates early neovascularisation (proliferation and migration of endothelial cells) via ET-RB receptors.4 The ET system also plays a less direct role in angiogenesis by, for example, breaking down the extracellular matrix.3,5 Studies have linked increased tumour vascularity to ET-1 in brain tumours, ovarian and colorectal cancer,4,6,7 and in a ...
The contribution of the endothelin system to BP regulation in the SHR is controversial, but the present work appears to be the first in which BP was measured by radiotelemetry. We found that bosentan per se failed to induce any change in BP in both rat strains. The bosentan was active because it antagonized the effects of exogenous administration of ET-1 in conscious rats (Fig 2⇑) and the tension responses to ET-1 in ring preparations of rat aorta (Table 2⇑) in a competitive fashion. These results parallel those of other researchers.6 7 In contrast to our findings with bosentan, both BQ-123, an ETA antagonist, and SB 209670, a nonselective ETA/ETB antagonist, have been reported to reduce BP in SHR8 9 and transgenic rats10 when infused over prolonged periods. On the other hand, other researchers have reported no change of BP with BQ-123 and bosentan in SHR.11 12 Pressure in these previous studies was monitored with exteriorized catheters or by the tail-cuff method. Control BP values are ...
Endothelin is the most potent constrictor of human blood vessels known to man. In mammals, there are three structurally and pharmacologically separate ET isopeptides: ET-1, ET-2, and ET-3 (Volpe 46). Endothelin-1 is the primary isoform in the human cardiovascular system and is a 21-amino acid peptide produced chiefly by endothelial cells (Lüscher 2434). Endothelin-converting enzymes (ECE), chymases, and non-ECE metalloproteases are responsible for the synthesis of ET-1 by means of autocrine regulation (Lüscher 2434). ET-1 operates through the initiation of two G-protein coupled receptors: ETA and ETB. Located on vascular smooth muscle cells, ETA receptors regulate vasoconstriction and cell proliferation. ETB receptors, situated on endothelial cells, mediate endothelium-dependent vasodilation through the release of nitric oxide and prostacyclin (Haapaniemi 721). In addition to its cardiovascular and mitogenic effects, endothelin-1 is involved in gastrointestinal and endocrine function, ...
We are interested in developing an airway explant culture system using sheep bronchi in which to establish respiratory viral infection and from which tissue can be used for functional, biochemical and immunohistochemical studies involving the endothelins (ETs). Freshly harvested sheep bronchial airway smooth muscle contains a homogeneous population of the ETA receptor. However, the potency of ET-1 and maximum contractile response of sheep bronchial explants to ET-1 increased with time in culture, despite these parameters remaining constant for carbachol in explants maintained for up to 48h. The possibility that this was caused by changes in ET receptor density was assessed using light microscopic quantitative autoradiography. In view of the increased responsiveness to ET-1 in cultured explants, it was surprising to demonstrate a significant decrease in total ET receptor (59±6% compared with the initial value, n = 4-5; P,0.01) and ETA receptor (51±2% compared with the initial value, n = 4-5, ...
Fingerprint Dive into the research topics of The endothelin-converting enzyme-1/endothelin-1 pathway plays a critical role in inflammation-associated premature delivery in a mouse model. Together they form a unique fingerprint. ...
Find Endothelin Receptors research area related information and Endothelin Receptors research products from R&D Systems. Learn more.
TY - JOUR. T1 - Increased plasma urotensin II levels in patients with diabetes mellitus. AU - Totsune, Kazuhito. AU - Takahashi, Kazuhiro. AU - Arihara, Zenei. AU - Sone, Masahiko. AU - Ito, Sadayoshi. AU - Murakami, Osamu. PY - 2003/1/1. Y1 - 2003/1/1. N2 - Urotensin II (UII) is the most potent vasoconstrictor peptide, whereas it acts as a vasodilator on some arteries. We studied plasma levels of UII in diabetic patients with normal serum creatinine levels (, 90 μmol/l) and the expression of UII and its receptor in cultured human vascular endothelial cells. Plasma UII levels were significantly elevated by 1.8-fold in diabetic patients without proteinuria (7.8±0.6 fmol/ml; P , 0.0001) and 1.7-fold in those with overt proteinuria (7.3±0.9 fmol/ml; P = 0.0018) when compared with healthy subjects (4.4±0.2 fmol/ml). No significant correlation was obtained between plasma UII levels and fasting blood sugar (P = 0.631 and P = 0.853 in non-proteinuric and proteinuric diabetic patients respectively), ...
Since its discovery in 1988, endothelin (ET) has been widely implicated in the pathophysiology of cardiovascular disease. ET antagonists have favourable effects in experimental models of these...
The IUPHAR/BPS Guide to Pharmacology. ETA receptor - Endothelin receptors. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Fingerprint Dive into the research topics of Affinity labelling of endothelin receptor and characterization of solubilized endothelin-endothelin‐receptor complex. Together they form a unique fingerprint. ...
Results Ninety-eight patients (initial ERA=24, initial PDE5=59, initial ERA/PDE5=15) were included; no significant differences in baseline variables existed. TTCW was significantly worse in patients initially started on ERA compared to PDE5 or ERA/PDE5 (p=0.0001). Baseline factors independently associated with shorter TTCW were initial ERA (HR 2.63, p=0.009), lower DLCO (HR 0.69 per 10% change, p=0.04), and higher PVR (HR 1.10 per Wood unit change, p=0.007). Three year survival was significantly worse in the initial ERA group (52.9%) compared to the PDE5 (91.5%) or ERA/PDE5 group (92.9%, p=0.004). The only baseline factor independently associated with risk for death in this cohort was initial ERA therapy (HR 4.55, p=0.004). ...
Ednrb - Ednrb (untagged ORF) - Rat endothelin receptor type B (Ednrb), (10 ug) available for purchase from OriGene - Your Gene Company.
Gentaur molecular products has all kinds of products like :search , Assaypro \ Endothelin_2, anti_human \ 10811-05015 for more molecular products just contact us
This will be short and sweet since all I did was….run. Sorry Ponies. Next week I swear. Because this months IRL is all about running, Ive decided to do a little pre-race interview…with myself. Running Tell me about your training… I ran just over 106 miles last month, which is consistent with the mileage I ran […] more. ...
How could a running club be virtual? So I Googled the term virtual race and was astounded at how many of them there were AND had amazingly geeky themes!
Asier Galan - Drosten irakasleak zientifikoki egiaztatu gabeko datuak erabili zituen bere 2019-nCoV PCR probarako eta, bere kideekin batera
Gure kantak eta ipuinak ezagutarazteko webgunea. Euskal Herriko Ahotsak proiektuan jasotako testigantzak, ahozko ondarea jaso eta zabaltzeko.
Gure kantak eta ipuinak ezagutarazteko webgunea. Euskal Herriko Ahotsak proiektuan jasotako testigantzak, ahozko ondarea jaso eta zabaltzeko.
Hainbat liztor espeziek arrautzak beste intsektu baten barruan txertatzen dituzte, eta bizirik daudela larbentzako bazka modura erabiliak izateko.
Jostura termo-zigilatuak dituen jaka iragazgaitza, 140 gramoko betegarri sintetikoarekin. Kremailera iragazgaitzak. Velcroz estutzeko eskumuturrak eta tankaz estutzeko barrenak.
... snowHeads ski club 2.0 is the friendliest ski club ever. Impartial snow reports from real people. Discussion board, ski club forum, snowboarding, off piste skiing
Endothelin-1 (Human, Rat, Porcine, Mouse, Canine, Bovine) 0 CNP-22 (Human, Porcine, Rat) 0 ...
  • ET exerts its effects through two types of endothelin receptors: type A (ETAR) and type B (ETBR). (springer.com)
  • Khodorova A, Montmayeur JP, Strichartz G. Endothelin receptors and pain. (springer.com)
  • Quantification of endothelin receptor subtypes in peripheral tissues reveals downregulation of ET(A) receptors in ET(B)-deficient mice. (springer.com)
  • Subtype-specific sorting of the ETA endothelin receptor by a novel endocytic recycling signal for G protein-coupled receptors. (springer.com)
  • Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. (springer.com)
  • Takigawa M, Sakurai T, Kasuya Y, Abe Y, Masaki T, Goto K. Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. (springer.com)
  • The endothelin receptor antagonists inhibit the binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells which results in vasodilation. (nih.gov)
  • Endothelin receptors are relatively enriched in pulmonary vasculature and their inibition results in a decrease in pulmonary vascular pressure. (nih.gov)
  • Two forms of endothelin receptors have been identified - type A (ETA) and type B (ETB). (nih.gov)
  • Endothelins are peptides with receptors and effects in many body organs. (wikipedia.org)
  • Endothelin functions through activation of two G protein-coupled receptors, endothelinA and endothelinB receptor (ETA and ETB, respectively). (wikipedia.org)
  • Endothelin receptors are present in the three pituitary lobes which display increased metabolic activity when exposed to ET-1 in the blood or ventricular system. (wikipedia.org)
  • The ubiquitous distribution of endothelin peptides and receptors implicates involvement in a wide variety of physiological and pathological processes among different organ systems. (wikipedia.org)
  • Receptors for endothelin-1 exist in brain neurons, indicating a potential role in neural functions. (wikipedia.org)
  • Endothelin receptors have also been found in the brain, e.g. cerebral cortex, cerebellum and glial cells [ PMID: 1847708 , PMID: 2156267 ]. (ebi.ac.uk)
  • ETA receptors are considered to be the primary vasoconstrictor and growth-promoting receptor, and the binding of endothelin to ETA increases vasoconstriction (contraction of the blood vessel walls) and the retention of sodium, leading to increased blood pressure [ PMID: 1351106 ]. (ebi.ac.uk)
  • Endothelins were also expressed in the arteries, and endothelin receptors were present on a subset of the SCG neurons. (sciencemag.org)
  • Collectively, the endothelins and their receptors--referred to as the endothelin (ET) axis--have key physiological functions in normal tissue, acting as modulators of vasomotor tone, tissue differentiation, development, cell proliferation and hormone production. (nih.gov)
  • The endothelin (ET) system, like other vascular regulatory systems, consists of a parent peptide that undergoes enzymatic activation and exerts its biologic effects by modulating specific receptors. (ahajournals.org)
  • This review focuses on the localization of endothelin receptors (ET A and ET B ) within the kidney, as well as the ET-1 functions through them. (mdpi.com)
  • Haendler B, Hechler U, Schleuning WD: Molecular cloning of human endothelin (ET) receptors ETA and ETB. (drugbank.ca)
  • Arai H, Nakao K, Hosoda K, Ogawa Y, Nakagawa O, Komatsu Y, Imura H: [Molecular cloning of human endothelin receptors and their expression in vascular endothelial cells and smooth muscle cells]. (drugbank.ca)
  • We studied nine lean and seven obese humans, measuring the metabolic and hemodynamic effects of insulin (300 mU · m −2 · min −1 ) alone and during femoral artery infusion of BQ123 (an antagonist of type A endothelin receptors, 1 μmol/min). (diabetesjournals.org)
  • Because endothelins have opposite vascular effects, possibly mediated by different receptors 1 , complete blockade of the actions of endogenous endothelins requires antagonism of both endothelin A and endothelin B receptors, as exerted by the combined nonpeptide blocker bosentan 26 . (ersjournals.com)
  • "Endothelin Receptors: ET A " . IUPHAR Database of Receptors and Ion Channels . (wikidoc.org)
  • Phosphorylation and desensitization of human endothelin A and B receptors. (wikidoc.org)
  • EDNRA and EDNRB (endothelin A and B receptors, respectively) are members of the rhodopsin-like 7-transmembrane receptor family. (rndsystems.com)
  • 6 This response has been attributed to stimulation of two subtypes of endothelin receptors: the ET A receptor, mediating vasoconstriction, and the ET B receptor, causing endothelium-dependent vasodilation (through a release of endothelium-derived relaxing factor [EDRF] and/or prostacyclin). (ahajournals.org)
  • This led for the search for antagonists of endogenous endothelin and, more precisely, for an antagonist of endothelin-1 receptors. (ahajournals.org)
  • We have previously reported a significant contribution of ETA- and ETB-receptors in the eicosanoid-releasing properties of endothelin-1 (ET-1) in the guinea-pig perfused lung. (lww.com)
  • These studies therefore aimed to characterize endothelin peptides and receptors ET A and ET B in human kidney, to direct potential therapeutic endeavours. (portlandpress.com)
  • 4. The identification of species differences between man and rat directed further development of quantitative molecular biological methodology to permit analysis of endothelin receptors in human renal biopsies, and demonstrated perturbation of the system in the context of cyclosporin A therapy in renal transplantation. (portlandpress.com)
  • Endothelin type B (ET B ) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk? (portlandpress.com)
  • 1996 Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. (springer.com)
  • These agents bind to endothelin receptors present in endothelium and vascular smooth muscle cells. (medscape.com)
  • Ambrisentan inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. (medscape.com)
  • Endothelin-1 (ET-1), a 21 amino acid residue originally characterised by Yanagisawa and colleagues, 1 acts via specific receptors and has both vasoactive as well as mitogenic effects. (bmj.com)
  • mice that are pharmacologically treated to block action of the two endothelin receptors ovulate fewer oocytes and form fewer corpora lutea. (illinois.edu)
  • The role of endothelin-1 (ET-1) and its receptors (ET-RA and ET-RB) in tumour development and progression involves complex interactions. (scielo.org.za)
  • Endothelin-1 (ET-1), together with its cognate receptors endothelin receptor subtype A (ET-RA) and endothelin receptor subtype B (ET-RB), is known to be one of the many mediators that play a role in angiogenesis. (scielo.org.za)
  • Up-regulation of contractile endothelin receptors by airborne fine particulate matter in rat mesenteric arteries via activation of MAPK pathway. (genetex.com)
  • The Role of MAPK Pathways in Airborne Fine Particulate Matter-Induced Upregulation of Endothelin Receptors in Rat Basilar Arteries. (genetex.com)
  • The ETA receptor is a member of the endothelin receptor group of G-protein-coupled receptors that also includes ETB. (cellsciences.com)
  • Introduction: Endothelin-1 (ET-1) is a potent vasoactive peptide that acts on ETA and ETB receptors and has been implicated in hemorrhagic shock (HS). (ovid.com)
  • These results suggest that central 2 -adrenoceptor mechanisms involved in clonidine-induced hypotension and bradycardia do not appear to be influenced by activation of endothelin receptors. (frontiersin.org)
  • In addition to the systemic circulation, endothelin production and endothelin receptors have been demonstrated in the central nervous system. (frontiersin.org)
  • In humans, endothelins mediate their actions via two specific G-Protein coupled receptors, ETAR and ETBR. (acris-antibodies.com)
  • The endothelin receptors differ in their ligand specificity. (acris-antibodies.com)
  • Until recently, it was thought that all cellular activities of the endothelins were mediated through their interactions with their cell surface receptors. (acris-antibodies.com)
  • Endothelins activate receptors to induce general vasoconstriction. (agscientific.com)
  • Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. (lu.se)
  • The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors. (lu.se)
  • A gene on chromosome 4q31.22 that encodes endothelin-A receptor, a member of the endothelin receptor group of G-protein-coupled receptors, located primarily in the vascular endothelial cells where they play a role in vasoconstriction, vasodilation, bronchoconstriction and cell proliferation. (thefreedictionary.com)
  • The endothelin system of peptides and their receptors have been implicated for their neurodegenerative role in glaucoma. (arvojournals.org)
  • Role of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. (springer.com)
  • Bagnato A, Loizidou M, Pflug BR, Curwen J, Growcott J. Role of the endothelin axis and its antagonists in the treatment of cancer. (springer.com)
  • Motte S, McEntee K, Naeije R. Endothelin receptor antagonists. (springer.com)
  • In patients with pulmonary arterial hypertension, (PAH) the endothelin receptor antagonists have been shown to improve exercise tolerance and slow progression of disease. (nih.gov)
  • Three endothelin receptor antagonists are currently approved and in use in the United States: bosentan (2001: Tracleer), ambrisentan (2007: Letairis) and macitentan (2013: Opsumit). (nih.gov)
  • While all endothelin receptor antagonists have been associated with occasional transient serum enzyme elevations during therapy, only bosentan and sitaxentan have been clearly linked to instances of clinically apparent, acute liver injury. (nih.gov)
  • The use of endothelin receptor antagonists in pulmonary arterial hypertension (PAH) is based upon the proposed pathogenesis of this disease, which is marked by enhanced synthesis of ET-1 and progressive proliferation and hypertrophy of smooth muscle cells in the pulmonary vasculature. (nih.gov)
  • In several randomized controlled trials, endothelin receptor antagonists were shown to decrease pulmonary vascular pressure and improve exercise tolerance and symptoms in patients with PAH. (nih.gov)
  • The endothelin receptor antagonists have been associated with a low, but appreciable rate of serum enzyme elevations during therapy that are generally transient and mild, but can cause mild symptoms and require dose modification or discontinuation. (nih.gov)
  • Several endothelin receptor antagonists have been associated with rare, but potentially severe instances of clinically apparent, acute liver injury. (nih.gov)
  • In addition, the endothelin receptor antagonists are teratogenic in animals. (nih.gov)
  • The three endothelin receptor antagonists are discussed separately with references appropriate for each agent. (nih.gov)
  • Textbook of hepatotoxicity published in 1999, before the availability of endothelin receptor antagonists). (nih.gov)
  • clinical features of liver injury due to the endothelin receptor antagonists are not specifically discussed). (nih.gov)
  • Therefore, endothelin receptor antagonists have been proposed as potential drug targets. (mdpi.com)
  • In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. (mdpi.com)
  • In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described. (mdpi.com)
  • Endothelin antagonists have demonstrated antifibrotic, anti-inflammatory, and antiproteinuric effects in experimental studies. (medscape.com)
  • Dipeptide sulfonamides as endothelin ETA/ETB receptor antagonists. (biomedsearch.com)
  • In this study, a series of potent dipeptide sulfonamide dual-endothelin ETA/ETB receptor antagonists were prepared to investigate their potential benefit in vascular diseases. (biomedsearch.com)
  • The Discovery of Sulfonamide Endothelin Antagonists and the Development of the Orally Active ET(A) Antagonist5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide, J. of Medicinal Chemistry, vol. 37, No. 3 (1994) pp. 329-331. (patentgenius.com)
  • Identification of a New Class of ET(A) Selective Endothelin Antagonists by Pharmacophore Directed Screening, Biochemical and Biophysical Research Comm. (patentgenius.com)
  • Endothelin receptor antagonists have been shown to increase forearm blood flow in humans 2 , 3 , to reduce brachial artery pressure in patients with essential hypertension 4 and to decrease pulmonary artery pressure in patients with primary pulmonary hypertension 5 , 6 . (ersjournals.com)
  • The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis. (hindawi.com)
  • Orally active endothelin antagonists are now being developed, but little was known of endothelin's role as a renal peptide in humans. (portlandpress.com)
  • This invention relates to endothelin antagonists useful, inter alia, for treatment of hypertension. (google.com)
  • BRIEF DESCRIPTION OF THE INVENTION ##STR2## and pharmaceutically acceptable salts, prodrugs and solvates thereof are endothelin receptor antagonists useful, inter alia, as antihypertensive agents. (google.com)
  • Orally acting ET antagonists appear very promising in clinical trials, particularly in patients with chronic heart failure and hypertension, but more information on the roles of the ET receptor subtypes in health and disease is required so that an informed choice can be made between the use of endothelin-A (ET-A) receptor-selective and nonselective receptor antagonists. (springer.com)
  • Clinical development of endothelin receptor antagonists. (springer.com)
  • Cyclic pentapeptide endothelin A receptor antagonists with attenuated in vivo clearance. (springer.com)
  • Pyrrolidine-3-carboxylic acids as endothelin antagonists: 3. (springer.com)
  • Collectively, our findings indicate that adjuvant trials with endothelin antagonists may be considered for patients with advanced bladder cancer following therapy of the primary lesion. (aacrjournals.org)
  • Endothelin-1 (ET-1) is a 21 amino acid peptide that acts in a paracrine and autocrine fashion as a potent vasoconstrictor. (nih.gov)
  • Endothelins are endothelium-derived vasoconstrictor peptides. (rcsb.org)
  • Endothelin (ET)-1 is a potent vasoconstrictor and mitogen, and because of these properties, it is thought to play a role in the development of hypertension. (ahajournals.org)
  • Endothelin-1 (ET-1) is a potent vasoconstrictor peptide apparently involved in a number of vascular diseases in man. (nih.gov)
  • The failure to show a vasoconstrictor effect of endogenous endothelins appears related, at least in part, to the release of nitric oxide (NO) by the endothelium, which either counteracts the effect and/or inhibits the synthesis of endothelins 16 - 19 . (ersjournals.com)
  • Endothelins are among the most potent vasoconstrictor proteins known. (clontech.com)
  • Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. (hindawi.com)
  • 1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and antinatriuretic effects of the endogenous vascular peptide endothelin. (portlandpress.com)
  • Inhalation of particulate matter (PM) air pollution has been shown to increase the release of vasoactive cytokines such as endothelin while individuals with vascular disease have augmented vasoconstrictor responses to this peptide. (epa.gov)
  • Endothelin-1 acts via two distinct receptor subtypes [endothelin-A (ET A ) and endothelin-B (ET B )] mediating the characteristic vasoconstrictor response upon activation by the peptide of vascular smooth muscle cells 2 . (nature.com)
  • Therefore, the objective of the present study was to investigate the regional and subregional changes in haemodynamics in response to the vasoconstrictor peptide endothelin-1 (ET-1) and MgSO 4 in more detail, using the coloured microsphere reference technique. (wiley.com)
  • Levels of endothelin-1 (ET-1), a potent vasoconstrictor, were affected by both RhoGDI2 reconstitution and tumor stage. (aacrjournals.org)
  • Mature endothelin-2 protein (EDN2) is a 21 amino acid peptide that is classically described as a potent vasoconstrictor. (illinois.edu)
  • Endothelin-1 (ET-1) is the most potent vasoconstrictor in the body. (dovepress.com)
  • In order to avoid the complication of the direct vasoconstrictor effects of endothelin-1, initial dose-response studies in animals treated with a ganglion blocker were performed. (frontiersin.org)
  • endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor ( 9 , 32 ) and consists of 21 amino acid residues with two intramolecular disulfide bonds. (physiology.org)
  • Secretion of endothelin-1 from the vascular endothelium signals vasoconstriction and influences local cellular growth and survival. (wikipedia.org)
  • Among numerous diseases potentially occurring from endothelin dysregulation are: several types of cancer cerebral vasospasm following subarachnoid hemorrhage arterial hypertension, pulmonary hypertension, and other cardiovascular disorders pain mediation cardiac hypertrophy and heart failure Dengue haemorrhagic fever Type II diabetes some cases of Hirschsprung disease In insulin resistance the high levels of blood insulin results in increased production and activity of ET-1, which promotes vasoconstriction and elevates blood pressure. (wikipedia.org)
  • The authors propose that smooth muscle cells of the external carotid artery may release endothelin, a neuropeptide better known for its vasoconstriction activity, which acts as a growth factor for axons of the SCG, guiding them to their salivary gland targets. (sciencemag.org)
  • Endothelin (2 nmol/kg) reduced renal flow (-86%) resulting from a vasoconstriction (+1,818%) significantly more pronounced than for the mesenteric vascular bed. (ahajournals.org)
  • In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ET A ) receptor. (mdpi.com)
  • The effects of endothelin receptor blockade on the pulmonary circulation have been reported variably, possibly in relation to a more or less important associated release of endogenous nitric oxide (NO). The aim of this study was to test whether endothelin antagonism would inhibit hypoxic pulmonary vasoconstriction, and if it would not, then would it do so after NO synthase inhibition. (ersjournals.com)
  • The authors conclude that endogenous nitric oxide is released by, and opposes the vasoconstricting effects of, endothelins in vivo , reducing systemic blood pressure and limiting hypoxic pulmonary vasoconstriction. (ersjournals.com)
  • Endothelins have been hypothesised to play a role in the mediation of hypoxic pulmonary vasoconstriction (HPV). (ersjournals.com)
  • EDNRA binds endothelins ET-1 and ET-2 preferentially, and is expressed on vascular smooth muscle where it mediates vasoconstriction. (rndsystems.com)
  • 1 2 3 4 5 Exogenous administration of endothelin-1 results in a biphasic response characterized by a transient vasodilation followed by a sustained vasoconstriction. (ahajournals.org)
  • To determine whether big-endothelin-1 (big-ET-1)-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123. (jci.org)
  • Vasodilator responses and endothelin-dependent vasoconstriction in metabolically healthy obesity and the metabolic syndrome. (sigmaaldrich.com)
  • Angiotensin II enhances endothelin-1-induced vasoconstriction through upregulating endothelin type A receptor. (genetex.com)
  • EDNRA encodes the bovine protein Endothelin-1 receptor (ETA), a peptide that plays a role in potent and long-lasting vasoconstriction. (cellsciences.com)
  • High ET-1 immunoreactivity has been shown in lamina propria and submucosa of patients with Crohn's disease and ulcerative colitis ( 19 ), and it has been suggested that local endothelin production by inflammatory cells may contribute to vasculitis in chronic inflammatory bowel disease by inducing intestinal ischemia through vasoconstriction ( 19 ). (physiology.org)
  • The active peptide is a ligand for endothelin receptor type B (EDNRB). (wikipedia.org)
  • The interaction of this endothelin with EDNRB is essential for development of neural crest-derived cell lineages, such as melanocytes and enteric neurons. (wikipedia.org)
  • Endothelin receptor type B , also known as ET B is a protein that in humans is encoded by the EDNRB gene . (wikidoc.org)
  • EDNRB binds all three endothelin forms equally, and is expressed on endothelial cells where it mediates vasodilation. (rndsystems.com)
  • Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. (springer.com)
  • genome-wide association studies in population of women in China: Data suggest that EDN3 (endothelin 3 ) and EDNRB (endothelin receptor type B (show EDNRB ELISA Kits )) play important roles in the molecular mechanisms underlying cervical cancer. (antibodies-online.com)
  • Enterocolitis causes profound lymphoid depletion in endothelin receptor B (show EDNRB ELISA Kits )- and endothelin 3 -null mouse models of Hirschsprung-associated enterocolitis. (antibodies-online.com)
  • Immunohistochemistry-Paraffin: EDNRB/Endothelin R Type B Antibody [NBP1-31108] - Paraffin-embedded Gingiva, using antibody at 1:100 dilution. (novusbio.com)
  • Western Blot: EDNRB/Endothelin R Type B Antibody [NBP1-31108] - A431. (novusbio.com)
  • Endothelin B Receptor antibody detects Ednrb protein at membrane on U87 xenograft by immunohistochemical analysis. (genetex.com)
  • Mutations in endothelin-ss- receptor gene (EDNRB) gene have been reported to cause Waardenburg syndrome (WS4) in humans. (thefreelibrary.com)
  • 2010). The syndrome has been associated with the mutations of Endothelin-B recpetor (EDNRB) gene (Puffenberger et al. (thefreelibrary.com)
  • The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. (nih.gov)
  • We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. (nih.gov)
  • What is the role of endothelin antagonist therapy in the treatment of diabetic nephropathy? (medscape.com)
  • Bosentan, an endothelin A and B receptor antagonist, did not affect baseline P pa , P pao or systemic arterial pressure ( P sa ) and did not alter HPV (n=8). (ersjournals.com)
  • To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs. (jci.org)
  • Bosentan is a dual endothelin A and B receptor antagonist for treatment of pulmonary arterial hypertension. (medscape.com)
  • Ambrisentan is an endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with World Health Organization (WHO) class II or III symptoms. (medscape.com)
  • Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. (unboundmedicine.com)
  • To test the hypothesis that the endothelin axis is important in lung metastasis, lung metastatic bladder carcinoma cells were injected in mice treated with the endothelin receptor-specific antagonist, atrasentan, thereby blocking engagement of the up-regulated ET-1 ligand with its cognate receptor. (aacrjournals.org)
  • Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). (lu.se)
  • 22, 2010 /PRNewswire-FirstCall/ -- Abbott (NYSE: ABT) today announced positive results from a Phase 2 dose-ranging study of atrasentan, a highly selective endothelin A receptor antagonist in development to help slow chronic kidney disease (CKD) progression in patients with type 2 diabetic nephropathy (diabetic kidney disease). (thefreedictionary.com)
  • Bakris noted that Gilead Sciences made a splash earlier this year when it released interim results showing dramatic additional blood pressure reductions with its selective endothelin A receptor antagonist darusentan in patients who had resistant hypertension despite maximal doses of a three-drug regimen that included a diuretic. (thefreedictionary.com)
  • The NDA for our lead drug candidate Thelin(TM) (sitaxsentan sodium), an endothelin A receptor antagonist for the treatment of PAH, is now under active review by the Cardio- Renal Division of the FDA. (thefreedictionary.com)
  • Derek's extensive background in launching new drugs, including pre-launch work on Zetia(R) and Clarinex(R), will be invaluable as we drive towards commercialization of sitaxsentan, our once daily, selective endothelin A receptor antagonist for the treatment of pulmonary arterial hypertension. (thefreedictionary.com)
  • SPP301 is a once daily oral endothelin A receptor antagonist that Speedel licensed from Roche in October 2000. (thefreedictionary.com)
  • a partnership formed by ICOS Corporation (Nasdaq:ICOS) and Texas Biotechnology Corporation (AMEX:TXB), announced that patients are being recruited for the STRIDE (Sitaxsentan To Relieve ImpaireD Exercise in pulmonary hypertension) Trial, a pivotal Phase 2/3 study with sitaxsentan, an oral endothelin A receptor antagonist. (thefreedictionary.com)
  • Endothelin-1 is the most powerful endogenous chemical affecting vascular tone across organ systems. (wikipedia.org)
  • Contribution of endogenous endothelin-1 to the maintenance of vascular tone: role of nitric oxide. (ebi.ac.uk)
  • Increased endogenous endothelin contributes to endothelial dysfunction in obesity and diabetes. (diabetesjournals.org)
  • Here, we test the hypothesis that increased endogenous endothelin action also contributes to skeletal muscle insulin resistance via impairments in insulin-stimulated vasodilation. (diabetesjournals.org)
  • These findings suggest that increased endogenous endothelin action contributes to insulin resistance in skeletal muscle of obese humans, likely through both vascular and tissue effects. (diabetesjournals.org)
  • Recent work from our laboratory and others has shown that increased endogenous endothelin activity in subjects with obesity and diabetes contributes to the impaired endothelium-dependent vasodilation that characterizes these states ( 7 , 8 ). (diabetesjournals.org)
  • However, whether endogenous endothelins play a role in the control of systemic and pulmonary vascular tone in vivo remains uncertain. (ersjournals.com)
  • In this study, the effects of endogenous endothelins on hyperoxic and hypoxic vascular tone, with and without NO synthase inhibition by N G -nitro‐ l ‐arginine ( l ‐NA), were examined. (ersjournals.com)
  • The goal of the present study was to evaluate the role of endogenous endothelin-1 in renal hypertension in dogs. (ahajournals.org)
  • Overproduction of endothelin in the lungs may cause pulmonary hypertension, which was treatable in preliminary research by bosentan, sitaxentan or ambrisentan. (wikipedia.org)
  • Green tea extract suppresses the oxidative stress and endothelin-1 expression associated with pulmonary fibrosis. (greenmedinfo.com)
  • Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism. (nih.gov)
  • We concluded that endothelin antagonism had minimal impact on gas exchange following APTE and confirmed our earlier observation that the main mechanism for hypoxemia in APTE was due to the mechanical redistribution of pulmonary regional blood flow away from the embolized vessels, resulting in the creation of many divergent low and high Va/Q regions. (nih.gov)
  • C. L. Golden, J. P. Kohler, H. S. Nick, and G. A. Visner, "Effects of vasoactive and inflammatory mediators on endothelin-1 expression in pulmonary endothelial cells," American Journal of Respiratory Cell and Molecular Biology , vol. 12, no. 5, pp. 503-512, 1995. (hindawi.com)
  • The endothelin system has been reported to be activated in various types of experimental or clinical pulmonary hypertension 1 . (ersjournals.com)
  • and 3) selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS, and heme oxygenase 1 are potential mechanisms of protection against hypoxic pulmonary hypertension in the CBDL-CH rats. (curehunter.com)
  • Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation. (jci.org)
  • These findings support the hypothesis that endothelin may play a role in modulation of high basal pulmonary vascular resistance in the normal fetus. (jci.org)
  • Such an up-regulation of the ET B -receptor pathway in the lungs, a tissue of high endothelial cell content, would support the decreased pulmonary tissue endothelin-1 levels observed in obese mice as a likely consequence of an accelerated clearance 6 . (nature.com)
  • No comments yet not if I possess to update your read pulmonary actions of the endothelins for a Party and you Please, we have a religion. (deadbatteries.com)
  • Most investigations on the haemodynamic effects of the endothelin system in humans were carried out in relation to systemic or pulmonary vascular beds, 9 13 while there are few data about coronary vascular effects in normal or diseased human hearts. (bmj.com)
  • Soler, M.J. Endothelin Blockade in Diabetic Kidney Disease. (mdpi.com)
  • To gauge its contribution to blood pressure regulation, we will induce endothelin blockade with acute systemic administration of BQ123 in an ascending dose regimen (25, 50, 100 and 300 nmol/min) and we will compare the hemodynamic effects between PAF and MSA patients. (bioportfolio.com)
  • To determine whether endothelin receptor A (Ednra, EDNRA, ETA) mediates EDN2 contractile action during ovulation, a conditional gene knockout approach was employed to selectively ablate Ednra in smooth muscle cells through a tamoxifen-inducible Cre recombinase system. (illinois.edu)
  • Serum concentrations of the 21 amino acid peptide endothelin ET1-21 were measured by radioimmunoassay. (bmj.com)
  • Here we set out to test the hypothesis that the vasoactive peptide endothelin (EDN) enables blood vessels to play such a role in indirectly linking activity and myelination. (elifesciences.org)
  • Selective endothelin-a receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. (springer.com)
  • These two subtypes of endothelin receptor are distinguished in the laboratory by the order of their affinity for the three endothelin peptides: the ETA receptor is selective for ET-1, whereas the ETB receptor has the same affinity for all three ET peptides. (wikipedia.org)
  • However, selective as well as nonselective endothelin receptor blockers have been shown to inhibit HPV in some studies 8 - 14 but not in others 15 , 21 - 23 . (ersjournals.com)
  • Nakano A , Kishi F , Minami K , Wakabayashi H , Nakaya Y , Kido H . 1997 Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acidlenght endothelins by chymase from human mastcells. (springer.com)
  • Cloning of a cDNA encoding a non-isopeptide selective subtype of the endothelin receptor. (springer.com)
  • Molecular cloning of a nonisopeptide- selective human endothelin receptor. (springer.com)
  • For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). (sigmaaldrich.com)
  • While ETAR has varying affinities for the endothelin isoforms (ET-1 >ET-2>ET-3), ETBR shows no selective affinity. (acris-antibodies.com)
  • TBC3711 is greater than 100,000-fold selective in the targeting of the endothelin A receptor versus the endothelin B receptor. (thefreedictionary.com)
  • Two endothelin receptor subtypes have been isolated and identified, endothelin A receptor(ETA) and endothelin B receptor (ETB) [ PMID: 12037137 , PMID: 1719979 , PMID: 1849646 , PMID: 1710450 ], and are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (GPCRA) which stimulate multiple effectors via several types of G protein [ PMID: 7882989 ]. (ebi.ac.uk)
  • Karet F, Kuc R, Davenport A. Novel ligands BQ 123 and BQ 3020 characterise endothelin receptor subtypes ETA and ETB in human kidney. (springer.com)
  • However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. (unboundmedicine.com)
  • We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. (unboundmedicine.com)
  • Plasma endothelin-1 levels, similar under basal conditions in healthy and hypertensive dogs, increased 30-fold with bosentan ( P =.0001). (ahajournals.org)
  • These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. (ersjournals.com)
  • Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test). (plos.org)
  • Endothelins have also been implicated in a variety of pathophysiological conditions associated with stress including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure [ PMID: 18758495 ]. (ebi.ac.uk)
  • The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. (ebi.ac.uk)
  • Involvement of endothelin in renal processes. (ahajournals.org)
  • First, endothelin provoked a sharp hypotension with tachycardia, vasodilation of the hindquarter, and a pronounced decrease in renal and mesenteric blood flows. (ahajournals.org)
  • Renal vascular bed exhibited a pronounced sensitivity to the vasoconstrictive effect of endothelin associated with changes in renal function. (ahajournals.org)
  • Animal studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal damage. (portlandpress.com)
  • 3. Ligand binding, immunocytochemical, radioimmunoassay and molecular biological studies were used to establish endothelin as a renal peptide in man. (portlandpress.com)
  • We have published in this journal a study investigating comprehensively the vascular responses in a mouse model of heterozygous endothelial overexpression of the endothelin-1 gene concluding that the latter in combination with obesity aggravates renal arterial dysfunction 1 . (nature.com)
  • The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). (unboundmedicine.com)
  • The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction. (ahajournals.org)
  • In human papillomavirus (HPV)-positive cervical cancer cells, the endothelin A receptor (ET A R) mediates an endothelin-1-induced mitogenic effect, thus representing a relevant target for antitumor therapy. (aacrjournals.org)
  • Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways. (springer.com)
  • Endothelin-3 is a protein that in humans is encoded by the EDN3 gene. (wikipedia.org)
  • The protein encoded by this gene is a member of the endothelin family. (wikipedia.org)
  • The multigenic disorder, Hirschsprung disease type 2, is due to mutation in endothelin receptor type B gene. (wikidoc.org)
  • Ceccherini I, Zhang A, Matera I, Yang G, Devoto M, Romeo G, Cass D (1995) Interstitial deletion of the endothelin-B receptor gene in the spotting lethal (sl) rat. (springer.com)
  • By contrast to the similarly low plasma peptide levels in lean and obese wild type mice and littermates with heterozygous endothelial over-expression of the prepro-endothelin-1 gene (TET het ) 1 on standard chow or high fat diet, endothelin-1 levels in the lungs were significantly higher ( Figure 1A ). (nature.com)
  • Endothelin-1 (ET-1) content in lungs [ n =5-12, as picograms per milligram (pg/mg) lung tissue] (A) of wild-type (WT) mice and littermates with heterozygous endothelial overexpression of the endothelin-1 gene (TET het ) on standard chow (lean) and after 30 weeks of high fat feeding (obese). (nature.com)
  • This may occur despite an augmented ET B -receptor mediated increase in vascular tone as seen in some peripheral arteries from obese animals, in particular in those of endothelin-1 gene overexpressing mice 1 and contribute to the less than expected vascular and metabolic phenotype. (nature.com)
  • Using DNA microarrays to monitor the changes in gene expression following restoration of RhoGDI2 expression, we identified several potentially targetable proteins, including the endothelin-1 ligand (ET-1), that were suppressed in the presence of RhoGDI2 protein. (aacrjournals.org)
  • Just prior to ovulation, the gene endothelin-2 (Edn2) is highly yet transiently expressed for a two-hour window. (illinois.edu)
  • Further work is required that will examine localised cellular gene expression of the endothelin system as well as its pro-invasive and angiogenic effects in breast cancer models. (scielo.org.za)
  • Penetrance of Novel Mutations of Endothelin-B receptor Gene in Pakistani Families with Waardenburg Syndrome. (thefreelibrary.com)
  • Endothelin, hypertension and chronic kidney disease: new insights. (springer.com)
  • The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases. (wikipedia.org)
  • Central obesity and hypertension: the role of plasma endothelin. (biomedsearch.com)
  • In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. (biomedsearch.com)
  • Overexpression of endothelins contributes to hypertension and heart disease. (clontech.com)
  • Background Endothelin-1, a vasoconstrictive peptide released by endothelium, may be involved in the pathophysiology of hypertension. (ahajournals.org)
  • Conclusions Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. (ahajournals.org)
  • This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. (ahajournals.org)
  • Although it is clear that endothelin-1 is involved in the pathophysiology of conditions such as myocardial ischemia, 10 11 cyclosporine nephrotoxicity, 12 13 and subarachnoid hemorrhage-induced vasospasm, 14 15 it is questionable whether endothelin-1 would play a role in arterial hypertension. (ahajournals.org)
  • Reports on plasma endothelin-1 concentrations in hypertension have been controversial, as they were found to be either normal or slightly elevated. (ahajournals.org)
  • regulation , pure autonomic failure and multiple system atrophy patients with supine hypertension will undergo a medication testing with the endothelin blocker, BQ123. (bioportfolio.com)
  • We hypothesize that endothelin (ET)-l contributes to the increased vascular resistance in pure autonomic failure patients with supine hypertension. (bioportfolio.com)
  • This approach would allow us to identify patients in whom supine hypertension is not driven by sympathetic tone and thus, better characterize the role of endothelin in the hypertension of these patients. (bioportfolio.com)
  • To gauge its contribution to blood pressure regulation, pure autonomic failure and multiple system atrophy patients with supine hypertension will undergo a medication testing with the endothelin blocker, BQ123. (clinicaltrials.gov)
  • Endothelin receptor dimers evaluated by FRET, ligand binding, and calcium mobilization. (springer.com)
  • This project will exploit a new set of endothelin ligand and receptor mutants to evaluate their individual and combined roles in nervous system development. (bath.ac.uk)
  • Its ligand, endothelin , consists of a family of three potent vasoactive peptides: ET 1 , ET 2 , and ET 3 . (wikidoc.org)
  • The binding of platelets to the endothelial cell receptor LOX-1 causes a release of endothelin, which induces endothelial dysfunction. (wikipedia.org)
  • The aims of this study were to examine the expression level of SCUBE2 in T2DM patients with dyslipidemia and its correlation with endothelial dysfunction marker, endothelin-1 (ET-1) in this group. (bioportfolio.com)
  • On www.antibodies-online.com are 20 Endothelin 3 (EDN3) ELISA Kits from 9 different suppliers available. (antibodies-online.com)
  • Additionally we are shipping Endothelin 3 Antibodies (84) and Endothelin 3 Proteins (6) and many more products for this protein. (antibodies-online.com)
  • They normally act in equilibrium with vasodilation mechanisms, but overexpression of endothelins can cause increased blood pressure, heart rate, and intestinal fiber constriction. (agscientific.com)
  • Endothelins are proteins that constrict blood vessels and raise blood pressure. (news-medical.net)
  • In another set of experiments, endothelin (2 nmol/kg) induced an increase in proteinuria, characterized by an increase in excreted albumin and by the appearance of proteins with molecular weights of 20,000-280,000. (ahajournals.org)
  • In vitro, sustained exposure of insulin-responsive cells to endothelin 1 (ET-1) induces insulin resistance ( 14 - 16 ). (diabetesjournals.org)
  • Endothelin induces insulin resistance in isolated rat soleus muscle strips ( 16 ), and studies of whole organisms have found similar effects of exogenous endothelin. (diabetesjournals.org)
  • Endothelin-1 Induces an Endothelin-A-Receptor-Dependent and. (lww.com)
  • Endothelin-1 secretion by alveolar macrophages in systemic sclerosis," American Journal of Respiratory and Critical Care Medicine , vol. 156, no. 5, pp. 1429-1435, 1997. (hindawi.com)
  • The central administration of endothelins modulates endocrine and cardiovascular regulation and behavior ( van den Buuse, 1997 ). (frontiersin.org)
  • Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C and phospholipase D, as well as cytosolic protein kinase activation. (ebi.ac.uk)
  • The hypothesis was that endothelin antagonism may inhibit HPV, but if not, would do so after NO synthase inhibition. (ersjournals.com)
  • Endothelin-1 contributes to increased vascular reactivity and tone under cardiovascular risk conditions including obesity in both humans and animal models 2 . (nature.com)
  • A recently published study in humans provided evidence of a major contribution of endothelin towards maintaining an increased peripheral vascular tone in CHF. (bmj.com)
  • It may play a role in reducing systemic ENDOTHELIN levels. (curehunter.com)
  • In vivo, in mice lacking expression of endothelin receptor A, the SCG axons were no longer extended along the external carotid arteries. (sciencemag.org)
  • Cloning and expression of a human endothelin receptor: subtype A". The American Journal of the Medical Sciences . (wikidoc.org)
  • A subtype of endothelin receptor found predominantly in the KIDNEY. (curehunter.com)
  • A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. (curehunter.com)
  • Endothelin (ET) is a peptide produced by cells in the blood vessels and has powerful vessel-constricting effects. (news-medical.net)
  • Endothelin constricts blood vessels and raises blood pressure. (wikipedia.org)
  • ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. (ebi.ac.uk)
  • Endothelin derived from blood vessels helps direct sympathetic neurons to their target organs. (sciencemag.org)
  • Current animal evidence indicates that infusion of endothelin-1 (ET-1), a naturally occurring signaling molecule released from blood vessels, is safe and very likely to trigger migraine aura in patients. (clinicaltrials.gov)
  • 1998 Endothelin-1 enhances thymocyte proliferation in monolaterally adrenalectomized rats with controlateral adrenocortical regeneration. (springer.com)
  • Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. (springer.com)
  • In preliminary research, injection of endothelin-1 into a lateral cerebral ventricle was shown to potently stimulate glucose metabolism in specified interconnected circuits of the brain, and to induce convulsions, indicating its potential for diverse neural effects in conditions such as epilepsy. (wikipedia.org)
  • Garvin J, Sanders K. Endothelin inhibits fluid and bicarbonate transport in part by reducing Na+/K+ ATPase activity in the rat proximal straight tubule. (springer.com)
  • The following antibody was used in this experiment: Endothelin B Receptor Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-27173, RRID AB_2544649. (thermofisher.com)
  • Endothelins stimulate the contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferens, stomach) and stimulate secretion in several tissues e.g., kidney, liver and adrenals [ PMID: 16340664 , PMID: 8480469 , PMID: 8466176 ]. (ebi.ac.uk)
  • Brown MA, Smith PL. Endothelin: a potent stimulator of intestinal ion secretion in vitro . (springer.com)
  • Endothelin type A receptor. (springer.com)
  • Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. (nature.com)
  • Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone spontaneously hypertensi. (biomedsearch.com)
  • Upregulation of SCUBE2 expression in dyslipidemic type 2 diabetes mellitus is associated with endothelin-1. (bioportfolio.com)
  • Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. (biomedsearch.com)
  • Although endothelin is mainly associated with its role in blood pressure control and cardiovascular diseases, it continues to appear in other physiological functions and diseases. (news-medical.net)
  • Endothelins have involvement in cardiovascular function, fluid-electrolyte homeostasis, and neuronal mechanisms across diverse cell types. (wikipedia.org)
  • Role of endothelin in cardiovascular disease. (ebi.ac.uk)
  • The endothelin (ET) system is comprised of 4 active ETs, with ET-1 being the predominant isoform in the cardiovascular system. (ahajournals.org)
  • Therefore, diesel exhaust-released endothelin could contribute to air pollution-induced cardiovascular events in sensitized individuals. (epa.gov)
  • Miyauchi T , Masaki T . 1999 Pathophysiology of endothelin in the cardiovascular system. (springer.com)
  • Since its discovery in 1988, endothelin (ET) has been widely implicated in the pathophysiology of cardiovascular disease. (springer.com)
  • Endothelin as a regulator of cardiovascular function in health and disease. (springer.com)
  • The endothelin system and its potential as a therapeutic target in cardiovascular disease. (springer.com)
  • Western Blot: Endothelin 3 Antibody [NBP1-33578] - Western blot analysis of Endothelin 3 on Raji lysates using NBP1-33578 at a dilution of 1:1000. (acris-antibodies.com)
  • Western blot analysis of Endothelin-3 Antibody (C-term) Cat. (acris-antibodies.com)
  • Immunohistochemical staining of Adrenal (Medulla) using anti-Endothelin B Receptor antibody SP4124P. (acris-antibodies.com)
  • Auricchio A, Casari G, Staiano A, Ballabio A (1996) Endothelin-B receptor mutations in patients with isolated Hirschsprung disease from a noninbred population. (springer.com)
  • Chakravarti A (1996) Endothelin receptor mediated signaling in Hirschsprung disease. (springer.com)
  • 1996 The endothelin peptides. (springer.com)
  • Goto K , Hama H , Kasuya Y . 1996 Molecular pharmacology and pathophysiological significance of endothelin. (springer.com)
  • In vitro, endothelin 3 promoted outgrowth of explanted SCG neurons. (sciencemag.org)
  • Big Endothelin-1 can be hydrolyzed by chymase to generate endothelin 1 (1-21) in vitro. (anaspec.com)
  • They found specific expression of mRNA encoding endothelin-converting enzyme (which converts precursors of endothelin into the active form). (sciencemag.org)
  • Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. (springer.com)
  • Endothelin-1, a 21-amino-acid peptide produced by vascular endothelium, 1 is endowed with vasoconstrictive, inotropic, and mitogenic properties. (ahajournals.org)
  • Endothelins (ET-1, 2, and 3) are considered to be very powerful vasoconstrictive substances. (acris-antibodies.com)
  • Endothelin receptor type B is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. (wikidoc.org)
  • Endothelin receptor type A , also known as ET A , is a human G protein-coupled receptor . (wikidoc.org)
  • Here we define a pathway in which endothelin, signalling through the G protein-coupled receptor endothelin receptor B and PKC epsilon, regulates the number of myelin sheaths formed by individual oligodendrocytes in mouse and zebrafish. (elifesciences.org)
  • Stimulation of mitogenesis in human thyroid epithelial cells by endothelin. (ebi.ac.uk)
  • 1990). "Generation of human endothelin by cathepsin E." FEBS Lett. (wikipedia.org)
  • Sakamoto A, Yanagisawa M, Sakurai T, Takuwa Y, Yanagisawa H, Masaki T: Cloning and functional expression of human cDNA for the ETB endothelin receptor. (drugbank.ca)
  • PA5-27173 targets Endothelin B Receptor in Western Blot and Immunohistochemistry - Paraffin applications and shows reactivity with Human, mouse and Rat samples. (thermofisher.com)
  • Inoue A , Yanagisawa M , Kimura S , Kasuya Y , Miyauchi T , Goto K , Masaki T . 1989 The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. (springer.com)
  • Carrier-protein conjugated synthetic peptide encompassing a sequence within the C-terminus region of human Endothelin B Receptor. (novusbio.com)
  • It is now known that there are three endothelin genes in the human genome (ET-1, ET-2, and ET-3 genes). (eurekaselect.com)
  • We investigated the endothelin system when two cell types, namely human dermal microvascular endothelial cells (DMVEC) and the human breast tumour cell line (MCF-7) were cultured together and when each was exposed to the metabolites/conditioned medium (CM) of the other. (scielo.org.za)
  • Human endothelial cell storage granules: a novel intracellular site for isoforms of the endothelin-converting enzyme. (semanticscholar.org)
  • In addition, we have shown that endothelin-1 is present in human atherectomy specimens and after mechanical pressure or after stretch endothelin-1 is released. (annals.org)
  • Because the precise immunopathological events occurring in appendicitis are not completely understood, possible local production of endothelin-1 (ET-1) in human appendix was investigated. (physiology.org)
  • The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. (lu.se)
  • Nussdorfer GG , Rossi GP , Malendowicz LK , Mazzocchi G . 1999 Autocrine-paracrine endothelin system in the physiology and pathology of steroid-secreting tissues. (springer.com)
  • Brock B , Gregersen S , Kristensen K , Thomsen JL , Buschard K , Kofod H , Hermansen K . 1999 The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells. (springer.com)
  • Endothelin-1 has vasoconstricting and proliferative properties that antagonize the effects of nitric oxide. (annals.org)
  • Furthermore, the regulation of endothelin-1 and the regulation of nitric oxide are linked. (annals.org)
  • In this study, the endothelin-1 (ET-1) and nitric oxide (NO) concentrations in slow coronary flow (SCF) patients were assessed before and at the peak of the exercise stress test and compared with the values from healthy controls. (go.jp)
  • Pharmacology and physiopathology of the brain endothelin system: an overview. (ebi.ac.uk)
  • Compounds of the formula ##STR1## inhibit endothelin, wherein: R is phenyl, naphthyl or biphenyl, each of which may be substituted. (patentgenius.com)
  • This receptor-mediated clearance mechanism is particularly important in the lung, which clears about 80% of circulating endothelin-1 [ PMID: 11067800 , PMID: 11264479 ]. (ebi.ac.uk)
  • De Carlo E , Milanesi A , Martini C , Maffei P , Sicolo N , Scandellari C . 2000 Endothelin-1 and endothelin-3 stimulate insulin release by isolated rat pancreatic islets. (springer.com)
  • Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. (wikipedia.org)
  • This role of endothelin-1 is unrelated to its plasma levels. (ahajournals.org)
  • Functional signaling of endothelin 3 (ET3) and its receptor B (ETRB) has been shown to be required for the development of neural crest (NC)-derived pigment cells in mouse, but the precise role of ET3 is not completely understood. (pnas.org)
  • OBJECTIVE To determine whether increased plasma concentrations of endothelin-1 (ET-1) and big endothelin (BET) play a role in the regulation of coronary circulation in patients with idiopathic dilated cardiomyopathy (IDCM). (bmj.com)
  • However, the pathophysiological role of raised plasma ET-1 and big endothelin (BET) concentrations in the progression of CHF in IDCM is unknown. (bmj.com)
  • The findings support a role for the endothelin system in endothelial cell and breast cancer cell invasion. (scielo.org.za)
  • The aim of this study was to elucidate the role of endothelin-1 (ET-1) in the pathophysiology of retinitis pigmentosa (RP). (dovepress.com)
  • Effects of ET-1 on splanchnic glucose production independent of glucagon or insulin appear to be a component of the effects of endothelin on insulin sensitivity ( 22 ), and using the minimal model approach, one group found that ET-1 infusion produced impairment in the acute pancreatic response to glucose rather than inducing peripheral insulin resistance ( 23 ). (diabetesjournals.org)
  • Not only are both circulating and tissue levels of endothelin-1 increased in patients with atherosclerosis, but the effects of endothelin-1 are enhanced in pathophysiologic states [1]. (annals.org)