Endothelin-induced contractions

The first compound with published detailed information which supports the claims for a specific ETg antagonist is IRL 1038, (20) [Cys -Cys ] ET-1 (11-21). This compound showed specific antagonist activity both in binding assays and in endothelin-induced contraction models. With ET-3 as agonist, 3 /M IRL 1038 antagonized the ETb receptor-mediated contraction of guinea-pig ileal and tracheal smooth muscle but did not affect the ET receptor-mediated contraction of rat aortic tissue [110]. 

C26. Curzen, N. P., Mitchell, J. A., Jourdan, K. B Griffiths, M. J. D., and Evans T. W., Endothelin-1-induced contraction of pulmonary arteries from endotoxemic rats is attenuated by the endo-helin-A receptor antagonist, BQ123. Crit. Care Med. 24,2007-2013 (1996). 

Endothelial cells and the kidneys play probably an important role in the longterm homeostasis as well as in the development of AD. Endothelial cells synthesize and release vasorelaxant and vasoconstrictor substances. The vasoconstrictor mediators, endothelins, were isolated, purified, sequenced, and cloned [100], The human endothelin receptor has seven membrane helices and is apparently G-protein-coupled. Endothelin-induced smooth muscle contraction involves the following processes activation of PLC, PIP2 hydrolysis, generation of 1,4,5-IP3, accumulation of DAG, mobilization of intracellular Ca2+ with facilitation of Ca2+ influx, activation of PKC, activation of PLA2 and arachidonic acid release, activation of PLD, and stimulation of Na+-H+... 

Endothelin-1-induced contractions were increased in the coronary circulation with age (Tschudi and Luscher 1995). 

In rabbit artery rings denuded of the endothe-hum and cultured with 0.3 p,M doxorubicin for 7 days, the contractions induced by noradrenaline, but not those induced by endothelin-1 or high lU, were strongly inhibited (Murata et al. 2001). This reaction was followed by a decrease in the induction of the ttiA-adrenoceptor without any change in the mRNA level. Inhibition of noradrenaline-induced contractions by doxorubicin was attenuated by superoxide dismutase (EC 1.15.1.1), and a,A-adrenoceptor protein expression recovered. 

Kawanabe Y, Masaki T, Hashimoto N. 2004. Involvement of epidermal growth factor receptor-protein tyrosine kinase transactivation in endothelin-1-induced vascular contraction. J Neuro-surg 100 1066-1071. 

Ledvina, M.A. Hart, J. Bina, S. ling, M. Muldoon, S. Endothelin plays a role in contractions of isolated pig pulmonary vessels induced by diaspirin cross-linked hemoglobin. J. Lab. Clin. Med. 1999,133, 478-487. 

CSA have an intrinsic capacity to stimulate direct contraction of animal and human mesangial cells, smooth vascular cells and resistance vessels with obvious consequence for renal function and hemodynamics. These effects are associated to augmented intracellular influx of calcium, impaired relaxation response of vascular wall to vasodilatory stimuli and endothelin-1 [16, 20, 91, 223, 244-249]. CSA-induced cultured mesangial cell contraction was prevented by mycophenolic acid [250]. 

Mesangial cells are contractile and a number of vasoactive peptides are shown to induce MC contraction in vitro such as angiotensin II, vasopressin, norepinephrine, endothelin-1, thromboxane, adenosine, and serotonin [55], The absence of podocyte markers such as nephrin, podocin, Wilms tumor-1 (WT1), and endothelial markers such as von Willebrand factor and PECAM-1, is recommended. 

Endothelin-1 (ET-1) is a small polypeptide with vasoconstrictive and mitogenic properties. ET-1 originates from endothelial cells and VSMCs, and induces the replacement of endothelial cells by neointimal SMC during arthro-sclerotic plaque formation. Induction of ET-1 expression in SMCs by HjOj-evoked oxidative stress is inhibited by resveratrol." Moreover, resveratrol pretreatment suppresses ET-1-mediated protein tyrosine phosphorylation and MAPK activation, leading to SMCs proliferation and contraction. ... 

---