The endothelin system:a novel therapeutic target in cardiovascular disease

Abstract

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide which is generated by the vascular endothelium. It was first described in 1988 by Yanagisawa and colleagues and has since become the focus of a great deal of research interest. As a result of its potent vasoconstrictor effects, ET-1 has been implicated as an important mediator of the raised peripheral vascular resistance associated with a number of cardiovascular conditions, notably heart failure, hypertension and renal failure. A number of endothelin receptor antagonists are currently in development as novel treatments for cardiovascular disease. These compounds have vasodilator effects in healthy volunteers and in patients with cardiovascular disease both in the presence and absence of existing treatments. Endothelin antagonists have also been shown to have beneficial effects on renal function and may be of value in the treatment of both chronic and acute renal failure. Although current treatments have proven effective in limiting disease progression and mortality, cardiovascular disease remains a significant public healthcare problem. The endothelin system provides an exciting therapeutic target for the development of new treatments for a number of cardiovascular diseases. The results from ongoing clinical trials are awaited with interest.