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that 1 mg/kg LPS intravenously had only minor effects on serum transaminase activities and had no lethal effects (unpublished results, Moreau and Lebrec, 2001).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

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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 ...

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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. ...

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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). ...

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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!

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