Heart failure and endothelin receptor antagonists.

Cardiac myocytes and vascular endothelial cells produce endothelin-1, which increases the contractility of cardiac muscles and of vascular smooth muscles. Endothelin-1 also exerts long-term effects, such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. In heart failure, the production of endothelin-1 is markedly increased in the failing heart. Here, evidence that an endothelin receptor antagonist is a useful new drug for the treatment of heart failure is discussed. Long-term treatment with an endothelin receptor antagonist greatly improves the survival rate of animals (rat, hamster, etc.) with chronic heart failure. This beneficial effect is accompanied by amelioration of left ventricular dysfunction. The myocardial endothelin system appears to be a novel and important target for therapeutic intervention in heart failure.