Since its discovery in 1988 the powerful vasoconstrictor endothelin-1 (ET-1) has been widely implicated in the pathophysiology of chronic kidney disease (CKD) as well as the cardiovascular disease with which it is associated. ET receptor antagonists have favourable effects in experimental models of these conditions and orally acting antagonists are now licensed for the treatment of pulmonary arterial hypertension. However, there is a paucity of human data regarding the role of ET-1 in CKD. In this thesis, I have therefore explored the utility of ET-1 as a biomarker in CKD, and, using selective ET receptor antagonists, the beneficial renal and cardiovascular effects of ET receptor antagonism in CKD. I have shown that as glomerular filtration rate (GFR) declines plasma ET-1 increases linearly whereas urinary ET-1 shows an exponential increase. Furthermore, urinary ET-1 may be a useful marker of disease activity in patients with lupus nephritis. Its levels are high in those with biopsy-proven ...
The literature shows an increase in endothelin-1 with increased levels of erythrocytes. There are also indications that inflammation and elevated endothelin-1 levels interact with erythropoiesis. In this study, the association of erythrocytes and endothelin-1 in women of different ethnicities was investigated. Blood pressure, vascular resistance, and C-reactive protein (P = 0.09) were significantly higher in the African women (n = 102) compared to the Caucasian women (n = 115), while arterial compliance was significantly lower in the African women with no significant differences for endothelin-1. In single, partial, and multiple regression analyses, there was a significant positive correlation between the red blood cell count and log endothelin-1 in the Caucasians while in the Africans there was a weak negative correlation. This is an indication that endothelin-1 might interfere with erythrocyte production in Africans with higher levels of inflammation ...
Hypertension is largely attributed to abnormal renal sodium handling; however, a growing body of evidence now suggests that primary abnormalities in vessels can also cause aberrations in blood pressure. Very often, the source of the abnormality resides in the endothelial cells that regulate the functional state of the entire vessel, and this knowledge has directed our search for new diagnostic and therapeutic targets. To date, the role of transcriptional mechanisms in blood pressure regulation is poorly characterized. In this study, we found that E2F2, a transcription factor involved in cell-cycle control, regulates blood pressure by modulating vessel contractility. This previously unknown function of E2F2 evolves from the unique role of the molecule in endothelial cells: suppression of endothelin-converting enzyme 1 (ECE-1). ECE-1 converts the inactive precursor molecule big endothelin-1 into the potent vasoconstrictor endothelin-1, and genetic deletion of E2F2 in mice was associated with both ...
Milk protein-derived peptides with angiotensin-converting enzyme (ACE) inhibitory activity can reduce blood pressure in hypertensive subjects. The lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) is an ACE-inhibitory peptide released by tryptic digestion from the milk protein beta-lactoglobulin. Its ACE-inhibitory activity is 100 times lower than that of captopril. The latter is known to inhibit the release of the vasoconstrictor endothelin-1 (ET-1) by endothelial cells. The effects of ALPMHIR on the endothelium are currently unknown. In this study, the influence of ALPMHIR on release of ET-1 by endothelial cells was investigated. The basal ET-1 release of the cells was reduced by 29% (p,0.01) in the presence of 1 mM ALPMHIR, compared to 42% (p,0.01) for 0.1 mM captopril. Addition of 10 U/ml thrombin to the incubation medium increased the release of ET-1 by 66% (p,0.01). Co-incubation of 10 U/ml thrombin with 1 microM captopril or with 0.1 mM ALPMHIR inhibited the stimulated ET-1 release by 45% ...
TY - JOUR. T1 - TRAF3IP2 mediates high glucose-induced endothelin-1 production as well as endothelin-1-induced inflammation in endothelial cells. AU - Padilla, Jaume. AU - Carpenter, Andrea J. AU - Das, Nitin A. AU - Kandikattu, Hemanth Kumar. AU - López-Ongil, Susana. AU - Martinez-Lemus, Luis A.. AU - Siebenlist, Ulrich. AU - DeMarco, Vincent G.. AU - Chandrasekar, Bysani. PY - 2018/1/1. Y1 - 2018/1/1. N2 - Hy-perglycemia-induced production of endothelin (ET)-1 is a hallmark of endothelial dysfunction in diabetes. Although the detrimental vascular effects of increased ET-1 are well known, the molecular mechanisms regulating endothelial synthesis of ET-1 in the setting of diabetes remain largely unidentified. Here, we show that adapter molecule TRAF3 interacting protein 2 (TRAF3IP2) mediates high glucose-induced ET-1 production in endothelial cells and ET-1-mediated endothelial cell inflammation. Specifically, we found that high glucose upregulated TRAF3IP2 in human aortic endothelial cells, ...
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Increased basal ET-1 release by NOS inhibitor was observed in only 2 of 9 studies with static cultures36,37 (Figure). Furthermore, in these 2 studies, the increased ET-1 release was determined after prolonged incubation with NOS inhibitor (ie, 637 and 24 hours36). Thus, the observed ET-1 release36,37 is not reflective of possible acute negative regulation of ET-1 release by NO.. Other studies failed to demonstrate increased ET-1 release after extended incubation (3-24 hours) with NOS inhibitor27,35,38-41 (Figure). Importantly, the general inability of NOS inhibitor to increase ET-1 release does not seem to be because of the failure of NOS inhibitor to decrease NO because NOS inhibitor for 8 hours decreased basal NO by 75% but did not increase ET-1 release41 (Figure; Figure S1).. The effect of NO inactivation on basal ET-1 release was also examined with oxyhemoglobin, which binds NO38,39,42,43 (Figure). Although exposure to oxyhemoglobin for 1 to 24 hours increased ET-1 release, it is likely that ...
Krishnaswamy and colleagues outline several mechanisms by which mast cells might contribute to plaque inflammation and rupture. Further work is needed to establish a direct role for mast cells in plaque instability. The hypothesis that plaque behavior could be favorably altered by preventing mast-cell degranulation or by inhibiting mast-cell proteases is intriguing but as yet unproven. Drs. Doherty and McMillen point out the several proatherogenic properties of endothelin-1. The work by Zeiher and coworkers (1) suggests that endothelin-1 is involved in the pathogenesis of acute coronary syndromes. However, evidence for endothelin-1 as an important determinant of plaque vulnerability and rupture is yet to come. With the introduction of endothelin-1 antagonists, an opportunity exists to further explore the role of endothelin-1 in the behavior of atherosclerotic plaques. If endothelin-1 antagonists do reduce coronary events, a central role for endothelin in promoting plaque instability could then ...
The effects of intravenous endothelin-1 (ET-1) on the ventilatory response to hypoxia were studied in healthy humans. Nine volunteers were each exposed twice to 4 hr eucapnic hypoxia. They received a continuous infusion of ET-1 during the ET-1 protocol and an infusion of saline during the control protocol. Plasma ET-1 levels and an index of ventilation were measured regularly. Hypoxia caused a rise in plasma ET-1 in the control protocol. Hypoxia also caused the index of ventilation to increase in both protocols, and this increase was greater in the ET-1 protocol than in the control protocol. These results are consistent with the hypothesis that ET-1 plays a role in controlling the ventilatory response to hypoxia in man.
TY - JOUR. T1 - Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade. AU - Hathaway, Catherine K.. AU - Grant, Ruriko. AU - Hagaman, John R.. AU - Hiller, Sylvia. AU - Li, Feng. AU - Xu, Longquan. AU - Chang, Albert S.. AU - Madden, Victoria J.. AU - Bagnell, C. Robert. AU - Rojas, Mauricio. AU - Kim, Hyung Suk. AU - Wu, Bingruo. AU - Zhou, Bin. AU - Smithies, Oliver. AU - Kakoki, Masao. PY - 2015/4/21. Y1 - 2015/4/21. N2 - We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular ...
Characterization of canine pericardial fluid endothelin-1 levels.: Recently, extremely high concentrations of endothelin-1 (ET-1) were detected in the pericardi
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Semantic Scholar extracted view of Increased sensitivity to endothelin-1 in spontaneously hypertensive rats is closely related to resting membrane potential by Tomohisa Ishikawa et al.
Aims: Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. Main methods: We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. Key findings: The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91 +/- 1.23pg/ml versus 0.63 +/- 1.03pg/ml, p,0.001; ET-1/creatinine ratio: ...
These findings demonstrate that acute exposure to vehicular source air pollutants results in upregulation of circulating and vascular factors associated with progression of atherosclerosis, mediated in part through activation of ET-1-ET(A) receptor pathways.
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)
Low levels of plasma endothelin-1 in patients with retinitis pigmentosa Hiroshi Ohguro1, Yukihiko Mashima2, Mitsuru Nakazawa31Department of Ophthalmology, Sapporo Medical University School of Medicine, 2Department of Ophthalmology, Keio University School of Medicine, 3Department of Ophthalmology, Hirosaki University School of Medicine, JapanPurpose: The aim of this study was to elucidate the role of endothelin-1 (ET-1) in the pathophysiology of retinitis pigmentosa (RP).Methods: Plasma ET-1 levels and ophthalmic features in 50 RP patients were compared with those in 20 healthy-eye control subjects. Plasma ET-1 concentrations were determined using a commercially available enzyme-linked immunosorbent assay kit.Results: Mean plasma ET-1 levels of RP patients (1.88 ± 0.56 pg/mL) were significantly lower than those of control subjects (2.30 ± 0.30 pg/mL, Mann-Whitney’s U test; P < 0.01). However, ET-1 concentrations varied markedly in each patient. Among RP patients, a significant
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 ...
The present study shows that antagonism of endogenous endothelin-1 produces marked decreases in aortic and ventricular systolic pressures in hypertensive dogs. These decreases persist for at least 1 hour after discontinuation of the drug, which could be explained by the 3-hour half-life of bosentan (M. Clozel, personal communication, 1994). Although systemic vascular resistances were not determined, it is likely that these changes resulted from peripheral vasodilation rather than from a depression in myocardial function. A significant decrease in filling pressures, as assessed by LVEDP and LAP, was observed. Both end-diastolic and systolic volumes also tended to decrease. Finally, indexes of cardiac performance, such as peak (+)dP/dt or myocardial segmental shortening, remained unchanged. The decrease in mean AOP in hypertensive dogs, which averaged 38 mm Hg, clearly suggests that endogenous endothelin-1 might play a role in the pathogenesis of renal hypertension. This role of endothelin-1 is ...
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays a key role in vascular homeostasis by modulating expression levels of the vasoconstrictor endothelin-1 (ET-1). Elevated ET-1 levels are associated with vascular diseases, and ET-1 expression is tightly regulated via GAPDH-mediated destabilization of its mRNA. Recent studies suggest GAPDH binding of adenine-uridine rich elements (AREs) in the 3-untranslated region (3-UTR) of the ET-1 gene leads to decreased mRNA stability. However, structural and mechanistic details underlying the GAPDH-mediated control of ET-1 expression are lacking. We sought to elucidate the structural and mechanistic details for the GAPDH-induced destabilization of ET-1 mRNA via electrophoretic mobility shift assay (EMSA), isothermal titration calorimetry (ITC), and x-ray crystallography. To identify specific GAPDH binding sequences, we constructed short RNA transcripts of the putative mRNA binding region. Utilizing ITC and EMSA, we obtained dissociation constants. We ...
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. ...
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 ...
Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i.d. 5.5mm) and human radial (i.d. 3.23mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1-10µM), macitentan (0.03-0.3µM) or ambrisentan (0.1-1µM). RESULTS: All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in both arteries. The Clark plot and analysis gave the following pKB values: bosentan, pulmonary artery 6.28±0.13 and ...
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 ...
Succinyl-(glu(9),ala(11,15))-endothelin-1 (8-21) 142569-99-1 safety info, Succinyl-(glu(9),ala(11,15))-endothelin-1 (8-21) chemical safety search, Chemical Succinyl-(glu(9),ala(11,15))-endothelin-1 (8-21) safety technical specifications ect.
TY - JOUR. T1 - Triglycerides impair postischemic recovery in isolated hearts. T2 - Roles of endothelin-1 and trimetazidine. AU - Monti, Lucilla D.. AU - Allibardi, Sonia. AU - Piatti, Pier Marco. AU - Valsecchi, Gianpietro. AU - Costa, Sabrina. AU - Pozza, Guido. AU - Chierchia, Sergio. AU - Samaja, Michele. PY - 2001. Y1 - 2001. N2 - There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and hyperinsulinemic (insulin concentration = 1.2 μmol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (PO 2 = 670 mmHg, pH 7.4, 37°C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6-9 rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal coronary flow), followed by 30 min of reperfusion. We found that ...
The purpose of this study was to investigate the effect of acute high intensity aerobic training on ANP and Endothelin-1 in inactive obese women. In order to nineteen obese women mean age± SD: 27.94± 3.30, mean weight ±SD: 88.13 ±7.28, mean height ±SD: 163.00± 4.91, mean BMI ±SD: 32.96± 3.13 selected and were randomly allocated to experimental and control groups. Experimental group performed a session acute aerobic exercise on ergometer at intensity 25w that increased every two minute 25w to workload and performed to exhaustion every subject. Samples blood were taken after 12 hours fasting, before and after of program training. For analyzed of biochemical variables used ELISA method and for analyses data used ANOVA. Results of this study showed that acute aerobic training causes significant increase in level of plasma ANP in obese women (p=0.006). But no significant differences observe in plasma level of Endothelin-1. Also, any significant difference didnt observe between pre and ...
in Equine Veterinary Journal (2003), 35(2), 190-6. Reasons for performing study: There is currently little published information about the effects of endothelin-1 (ET-1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary ... [more ▼]. Reasons for performing study: There is currently little published information about the effects of endothelin-1 (ET-1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary vasculature and airways or which ET receptor subtypes mediate ET-1 induced vasoconstrictive and bronchoconstrictive action in the horse. Objectives: To investigate the effect of endothelin-1 (ET-1) on smooth muscle from isolated equine pulmonary artery and bronchus. In addition, the roles of ETA and ETB receptors in ET-1 mediated contraction in these tissues were assessed. Methods: The force generation of ring segments from pulmonary arteries or third-generation airways (obtained from horses subjected to euthanasia for orthopaedic ...
INTRODUCTION: The aim of our study was to analyse the role of adrenomedullin (AM) and endothelin-1 (ET-1) in the adaptation of the maternal vascular system in normotensive pregnancy. METHODS: Twenty-eight pregnant women, who were normotensive through
TY - JOUR. T1 - The role of endothelin-1 during ischemia-reperfusion injury. AU - Chang, H.. AU - Wu, G. J.. AU - Wang, S. M.. AU - Hung, C. R.. PY - 1992. Y1 - 1992. UR - http://www.scopus.com/inward/record.url?scp=0027075162&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0027075162&partnerID=8YFLogxK. M3 - Article. C2 - 1363641. AN - SCOPUS:0027075162. VL - 91. SP - 1182. EP - 1188. JO - Journal of the Formosan Medical Association. JF - Journal of the Formosan Medical Association. SN - 0929-6646. IS - 12. ER - ...
Sigma-Aldrich offers Sigma-E6139, Big Endothelin 2 human for your research needs. Find product specific information including CAS, MSDS, protocols and references.
The protein encoded by this gene is a member of the endothelin family. Endothelins are endothelium-derived vasoactive peptides involved in a variety…
Correspondence to Dr. Masakazu Haneda, The Third Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga, 520-2192, Japan. Phone: 81-77-548-2222; Fax: 81-77-543-3858; E-mail: haneda{at}belle.shiga-med.ac.jp ...
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology. (Endocrine Pathology) ...
R. Wang, ,, Fischer, K., W Dashwood, M., Greenwood, J. A., Ho, E., Williams, D. E., Ashktorab, H., Dashwood, M. R., and Dashwood, R. H., "Epigenetic inactivation of endothelin-2 and endothelin-3 in colon cancer.", International journal of cancer. Journal international du cancer, vol. 132, no. 5, pp. 1004-12, 2013. ...
Endothelin-1 (ET-1) has been demonstrated to play a role in many physiological processes including vasoconstriction, cardiovascular homeostasis, inflammation, angiogenesis, and tissue regeneration. A critical step in the ...
The potent vasoconstrictor endothelin-1 (ET-1) is at its highest concentration in the normal human ejaculate and is associated with the progression of metastatic prostate cancer. ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. The ETA-selective receptor antagonist A-127722 inhibits ET-1-stimulated growth, but the ETB-selective receptor antagonist BQ-788 does not. ET-3, an ETB-selective agonist, also had no effect on prostate cancer growth. No specific ETB-binding sites could be demonstrated in any established human prostate cancer cell line tested, and ETB mRNA, detected by reverse transcription PCR, was reduced. The predominance ...
TY - JOUR. T1 - Renal vasoconstriction to endothelin-1 is enhanced with blockade of endothelin-B receptors or nitric oxide production. AU - Stacy, D. L.. AU - Martinez, R.. AU - Tilton, Ronald. PY - 1996. Y1 - 1996. N2 - Endothelin (ET-1) is a potent renal vasoconstrictor causing an initial transient vasodilation due to activation of ETB receptors and a long-lasting vasoconstriction thought to be due to ETA and ETB receptors. In anesthetized rats ET-1 was infused intravenously {i.V., 1 nmole/kg) after BQ-123 (an ETA receptor antagonist), BQ-788 (an ETB receptor antagonist), or vehicle. Left renal artery flow and mean arterial pressure (MAP) were measured. Resistance was calculated as MAP/flow. ET-1 increased renal resistance by 248% (26±2 to 90±13 mmHg/ml/min.). After pretreatment with BQ-123 (1 mg/kg, i.V.), the increase in renal resistance with ET-1 was reduced by 77% (29±5 to 43±7 mmHg/ml/min.), due to a reduction in the increase in MAP by 81% and decrease in flow by 61%. Pretreatment ...
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 ...
Endothelin-1, angiotensin II, and oxygen-derived radicals are pivotal factors in the development and progression of atherosclerosis. In vitro studies suggest that generation of oxygen-derived radicals by angiotensin II is an important mechanism increasing endothelin-1 synthesis, which consecutively may trigger effects such as cell proliferation and hypertrophy. The aim of this study was to confirm our previous data in an ex vivo and an in vivo setting.. Explanted segments of internal mammary arteries were analyzed for big endothelin-1 expression following incubation with xanthine oxidase, angiotensin II, superoxide dismutase, and catalase to stimulate or to specifically inactivate oxygen-derived radicals. Endothelin-1 concentrations were determined by immunostaining and enzyme-linked immunosorbent assay. Further, oxypurinol was given to patients undergoing coronary angioplasty, a procedure known to increase plasma endothelin-1 concentrations.. Angiotensin II and xanthine oxidase dose-dependently ...
The BP-lowering effects of nebivolol are well established.13,27,28 The seminal and novel finding of the present study, however, is that in addition to, and independent of, lowering BP, nebivolol markedly and favorably affects ET-1 system activity. Indeed, the results reported herein demonstrate that (1) chronic nebivolol, but not metoprolol, therapy reduces ET-1-mediated vasoconstrictor tone in adults with elevated BP and (2) reductions in ET-1 vasoconstriction underlie nebivolol-induced improvements in endothelium-dependent vasodilation. Diminished ET-1-mediated vasoconstrictor tone may represent an important endovascular pleiotropic effect of nebivolol, contributing to its favorable effect on overall cardiovascular risk.29. In this study, there was a similar and significant (≈30%) increase in FBF responses to selective ETA receptor blockade in all 3 groups before treatment. In addition, nonselective ETA/B receptor blockade resulted in a further increase (≈35%) in FBF in all the groups. ...
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 ...
Using Na+/Ca2+ exchanger (NCX1)-deficient mice, the pathophysiological role of Ca2+ overload via the reverse mode of the Na+/Ca2+ exchanger in ischaemia/reperfusion-induced renal injury was investigated. Since NCX1-/- homozygous mice die of heart failure before birth, we utilized NCX1+/- heterozygous mice. The ischaemia/reperfusion-induced renal dysfunction in heterozygous mice were significantly attenuated compared with cases in wild-type mice. Also, histological renal damage such as tubular necrosis and proteinaceous casts in tubuli in heterozygous mice were much less than that in wild-type mice. Ca2+ deposition in necrotic tubular epithelium was observed more markedly in wild-type than in heterozygous mice. The increase in renal endothelin-1 (ET-1) content was significantly greater in wild-type than in heterozygous mice, and this reflected the difference in immunohistochemical ET-1 localization in necrotic tubular epithelium. We conclude that Ca2+ overload via the reverse-mode of Na+/Ca2+ ...
Endothelial cells were isolated from bovine thoracic aorta and cultured. Bovine aortic endothelial cells (BAEC) were incubated with radiolabeled arachidonic acid (3H-AA) or eicosapentaenoic acid (14C-EPA) (1 microM) for 3 hr. Both fatty acids were predominantly incorporated into phosphatidylcholine (57 +/- 2% and 62 +/- 2% respectively) and slightly into phosphatidylethanolamine (11 +/- 0.5% and 12 +/- 0.6% respectively). phosphatidylinositol (26 +/- 1.5% and 10 +/- 0.5% respectively) and neutral lipids (6 +/- 0.5% and 15 +/- 1% respectively). After BAEC incubation with 3H-AA for 24 hr with or without EPA (1 microM), the release of radioactive metabolites of AA induced by thrombin (5.5 U/ml) was strongly reduced by the preliminary treatment with EPA (72 +/- 5%). After BAEC incubation with AA, EPA or vehicle (control), endothelin-1 levels were measured by RIA in the culture medium and we observed that: 1) the basal production of endothelin-1 was not modified after either AA or EPA treatment, 2) the
Various tissues including heart express specific binding sites for endothelin. Endothelins have been reported to increase the force of contraction of cardiac muscle, presumably via specific receptors. Specific binding of endothelin to atrial tissue is particularly high. In spontaneously contracting rat atrial cells used in this study, all three isoforms of endothelin (endothelin-1, endothelin-2, and endothelin-3) decreased the rate of beating and caused an increase in inwardly rectifying K+ current in voltage-clamped whole cells. Endothelin-3 was the most potent isoform, and its effects on beating rate and K+ current were present at a concentration as low as 100 pM (Kd, approximately 1 nM). the atrial cells did not have the hyperpolarization-activated current (the pacemaker current), If. In excised inside-out patches, all three isoforms of endothelin activated a population of K+ channels with kinetic properties identical to those of acetylcholine (muscarinic)-activated K+ channels, and this was ...
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, ...
The major findings of this study are that ET-1 prevents apoptosis induced by serum deprivation in a dose-dependent manner via an ETA receptor in H9c2 cardiomyocytes and that the antiapoptotic effect of ET-1 is mediated through a c-Src/Bcl-xL pathway. Evidence for this proposal includes the following: (1) ET-1, but not AII, prevented mitochondrial cytochrome c release and apoptosis induced by serum deprivation in a dose-dependent manner, and this antiapoptotic effect was inhibited by an ETA receptor antagonist (BQ123) but not by an ETB receptor antagonist (BQ788); (2) the inhibitory effects of ET-1 on apoptosis were inhibited by tyrosine kinase inhibitors and adenovirus-mediated overexpression of KI-c-Src; (3) ET-1 stimulated c-Src activation; and (4) ET-1 upregulated an antiapoptotic molecule, Bcl-xL, and this upregulation was inhibited by tyrosine kinase inhibitors or cotransfection with KI-c-Src.. Recent evidence suggests that apoptosis of cardiac myocytes is a feature in cardiovascular ...
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. ...
Pathology: 1997-1998. ARMSTRONG, R.. Atkison, P.R., G.I. Joubert, C.M. Guiraudon, R. Armstrong, W. Wall, S. Asfar, and D. Grant. 1997. Arteritis and increased intracellular calcium as a possible mechanism for tacrolimus-related cardiac toxicity in a pediatric transplant recipient. Transplantation 64 (5): 773-775.. CHAKRABARTI, S.. Adams, P.C., and S. Chakrabarti. 1998. Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria. Gastroenterology 114 (2): 319-323.. Chakrabarti, S., X.T. Gan, A. Merry, M. Karmazyn, and A.A.F. Sima. 1998. Augmented retinal endothelin-1, endothelin-3, endothelinA and endothelinB gene expression in chronic diabetes. Current Eye Research 17: 301-307.. Chakrabarti, S., and A.A.F. Sima. 1997. Endothelin-1 and endothelin-3-like immunoreactivity in the eyes of diabetic and non-diabetic bb/w rats. Diabetes Research and Clinical Practice 37: 109-120.. Deng, D.X., S. Chakrabarti, M.P. Waalkes, and M.G. Cherian . 1998. Metallothionein and ...
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 ...