Effects of endothelin on intracellular Ca2+ and contractility in single ventricular myocytes from the ferret and human

We investigated the role of endothelin-1 on peak intracellular Ca2+ ([Ca2+]i) and peak shortening of ventricular myocytes (loaded with indo-1/AM) from failing human hearts. 10 nM of ET-1 significantly increased the cell peak shortening (84 +/- 29%, P less than 0.05) without significantly increasing the peak [Ca2+]i (15 +/- 7%, P greater than 0.05). Further studies on ferret cardiac myocytes indicated that in addition to producing dose-dependent (0.1-10 nM) significant increases in peak shortening (max 55 +/- 6% P less than 0.01) and non-significant increases in peak [Ca2+]i (max 35 +/- 19%, P greater than 0.05), endothelin-1 significantly shifted the peak [Ca2+]i-peak shortening curve upward. The results suggest that endothelin-1 acts directly on human and ferret cardiac myocytes to produce a positive inotropic effect that may predominantly be due to an enhanced myofilament Ca2+ responsiveness.