Functional Effects of Endothelin and Regulation of Endothelin Receptors in Isolated Human Nonfailing and Failing Myocardium

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An activated endothelin (ET) system may be of pathophysiological relevance in human heart failure. We characterized the functional effects of ET-1, ET receptors, and ET-1 peptide concentration in left ventricular myocardium from 10 nonfailing hearts (NF) and 27 hearts in end-stage failure due to idiopathic dilative cardiomyopathy (DCM).


ET-1 exerts inotropic effects in human myocardium through ETA receptor-mediated increases in myofibrillar Ca2+ responsiveness. In DCM, functional effects of ET-1 are attenuated, but ETA receptor density and ET-1 peptide concentration are increased, indicating an activated local cardiac ET system and possibly a reduced postreceptor signaling efficiency. (Circulation. 1999;99:1802-1809.)

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