Endothelin-1: a new target of therapeutic intervention for the treatment of heart failure

Endothelin-l has been appreciated in animals and humans as a potential targ et for inhibition in patients with acutely decompensated congestive heart f ailure (CHF), as well as patients with a chronic low-output state. There ha s been intense interest in determining the effects of endothelin-l on the c ardiovascular system. Elevated plasma levels of endothelin-l in patients wi th CHF portend a poorer prognosis than similar patients without elevated le vels. Endothelin-l levels correlate inversely with maximum oxygen consumpti on, and inhibition of the myocardial endothelin pathway in rats with CHF im proves survival. An association between endothelin-l and the development of CHF has recently been supported. Selectively inhibiting the endothelin A r eceptors in dogs with CHF produced hemodynamic improvement. Similarly, in r abbits, a structural advantage was demonstrated. Benefits in cardiac remode ling have been demonstrated in several models of CHF by nonselectively anta gonizing endothelin receptors, In human trials using nonselective endotheli n-l inhibitors, researchers have demonstrated hemodynamic benefit and impro vement in cardiac function in patients with decompensated CHF. Inhibition o f endothelin-l in patients with CHF appears to have potential therapeutic v alue, and ongoing clinical trials will further investigate the safety, effi cacy, and role of this new potential therapeutic target for the treatment o f CHF. (C) 2000 Lippincott Williams & Wilkins, Inc.