Endothelin-1 and endothelin receptor antagonists in cardiovascular remodeling

Endothelins build a peptide family composed of three isoforms, each of them containing 21 amino acids. Endothelin-1 is the isoform mainly responsible for any cardiovascular action and therefore the sole scope of this review. Endothelin-1 is the most potent endogenous vasoconstrictor known; in additi on it acts as a potent (co)mitogen. There is a substantial body of experime ntal evidence that endothelin-1 may contribute not only to sustained vasoco nstriction, but also to remodeling within the cardiovascular system. Thus, with the help of endothelin receptor antagonists (available for a few years ) the involvement of mainly ETA receptors in structural diseases such as he art failure, pulmonary hypertension, atherosclerosis, restenosis, systemic hypertension, and chronic renal failure has been shown. These data make end othelin receptor antagonists, and especially those selective for the ETA re ceptor, promising agents for the treatment of chronic cardiovascular diseas es associated with remodeling. Currently several chemically distinct, orall y available members of this novel class of therapeutic agents are under cli nical investigation.