The possible involvement of endothelins in a variety of diseases has attracted the attention of many pharmacologists in search of a novel therapeutic approach. The rapid development of endothelin research has resulted in the molecular characterization and pharmacological recognition of ETA and ETB receptors, and in the development of compounds selective for these receptors. However, the charact...

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-...

Porcine endotoxin shock is characterized by pulmonary hypertension, decreased mean arterial pressure and deteriorated cardiac performance. These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. Previous studies have shown that both the pulmonary and systemic circulation are improved by combined endothelinA- and endothelinB-receptor antagonism. This study was ...

RES-1149-1 and -2, produced by Aspergillus sp. RE-1149, were found to be non-peptidic antagonists for endothelin type B receptor (ET(B) receptor). RES-1149-1 and -2 selectively inhibited the endothelin-1 (ET-1) binding to ET(B) receptor in a competitive manner with IC50 values of 1.5 microM and 20 microM, respectively. RES-1149-1 inhibited the increase in intracellular Ca2+ concentration elicit...

Endothelial cells regulate vascular tone largely by the actions of endothelin-1. Endothelin-1 is a potent vasoconstrictor, with effects that are dependent on the receptors to which it binds as well as their location. Endothelin-1 dysregulation is implicated in pathological conditions, including those of the pulmonary vasculature and the kidney. In this review, we describe the physiology and act...

The endothelins (ETs) are peptides that have a diverse array of functions mediated by two receptor subtypes, the endothelin A receptor (ET(A)R) and the endothelin B receptor (ET(B)R). Pharmacological studies have suggested that in peripheral tissues, ET(A)R expression may play a role in signaling acute or neuropathic pain, whereas ET(B)R expression may be involved in the transmission of chronic...

An accumulating body of evidence indicates that an increased endothelin-1 level is related to endothelial dysfunction in cardiovascular diseases. In this study, we tested whether prolonged treatment of aortas with endothelin-1 induces endothelial dysfunction. When isolated aortas from control rats were cultured with endothelin-1, at levels above the plasma concentration, the acetylcholine-induc...

ENDOTHELIN-l (ET-l), a 21 amino acid peptide with potent vasoconstrictive properties has been implicated in the development of acute allograft rejection.) It is primarily produced by endothelial cells and its secretion, during acute rejection episodes, has been shown to be upregulated by TGFf3 and other proinflammatory cytokines released by graft infiltrating cells.) Additionally, ET-l has also...