Affiliation:
1. Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912;
Abstract
First identified as a powerful vasoconstrictor, endothelin has an extremely diverse set of actions that influence homeostatic mechanisms throughout the body. Two receptor subtypes, ETA and ETB, which usually have opposing actions, mediate the actions of endothelin. ETA receptors function to promote vasoconstriction, growth, and inflammation, whereas ETB receptors produce vasodilation, increases in sodium excretion, and inhibit growth and inflammation. Potent and selective receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contradictory and complicated because of the tissue-specific vasoconstrictor actions of ETB receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo. Considerable questions remain regarding whether ETA-selective or nonselective ETA/ETB receptor antagonists would be useful in a range of clinical settings.
Cited by
249 articles.
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