Mechanism of the Inotropic Action of Endothelin on the Ferret and Human Heart

Endothelin increases cardiac contractility by enhancing Ca2+ responsiveness with little or no increase in intracellular Ca2+. The increased Ca2+ responsiveness caused by endothelin is due to cytoplasmic or membrane alterations mediated by the endothelin receptor-second messenger system. Presently, there are no clinically available drugs that increase inotropy by enhancing myocardial responsiveness to Ca2+. Further delineation of the mechanisms by which endothelin enhances myocardial responsiveness to Ca2+ could lead to new pharmacological therapies for the acute and chronic treatment of patients with left ventricular systolic dysfunction.