Endothelin receptor antagonists and cardiovascular diseases of aging

Our understanding of the role of the endothelin system in human cardiovascu lar physiology and pathophysiology has evolved very rapidly since the initi al description of its constituent parts in 1988. Endothelin-1 (ET-1) is the predominant endothelin isoform in the human cardiovascular system and has potent vasoconstrictor, mitogenic and antinatriuretic properties which have implicated it in the pathophysiology of a number of cardiovascular disease s. The effects of ET-1 have been shown to be mediated by 2 principal endoth elin receptor subtypes: ETA and ETB. The development of a range of peptidic and nonpeptidic endothelin receptor antagonists represents an exciting breakthrough in human cardiovascular the rapeutics. Two main classes of endothelin receptor antagonist have been dev eloped for possible human therapeutic use: ETA-selective and nonselective a ntagonists. Extensive laboratory and clinical research with these agents ha s highlighted their promise in various cardiovascular diseases. Randomised, placebo-controlled clinical trials have yielded very encouraging results i n patients with hypertension and chronic heart failure with more preliminar y data suggesting a possible role in the treatment and prevention of athero sclerosis and stroke. Much more research is needed, however, before endothe lin receptor antagonists can be considered for clinical use.