Key result
Endothelin-1 increases peak shortening ~84% in failing human ventricular myocytes without raising peak intracellular Ca2+.
Endothelin-1 produces a positive inotropic effect in human and ferret ventricular myocytes, likely through enhanced myofilament Ca2+ responsiveness rather than increased intracellular Ca2+.
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May support Ca2+-independent inotropy in failing human myocytes; leaves open endothelin-1 as a therapeutic target in HF.
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.
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Qiu et al. (1992) studied Failing human hearts. Endothelin-1 was evaluated on Cell peak shortening and peak intracellular Ca2+ (p=<0.05). Endothelin-1 (10 nM) significantly increased cell peak shortening by 84% (P<0.05) without significantly increasing peak intracellular Ca2+ in ventricular myocytes from failing human hearts.
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