Endothelin Antagonism In The Treatment Of Heart Failure

Cardiac myocytes and vascular endothelial cells produce endothelin-1, which increases the contractility of cardiac muscle and of vascular smooth muscle. Endothelin-1 also has long-term effects, such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. The production of endothelin-1 is markedly increased in the failing heart. We discuss evidence favoring the use of an endothelin receptor antagonist as a new drug for heart failure. Long-term treatment with an endothelin receptor antagonist greatly improves the survival rate of animals (rats, hamsters, 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.