Pharmacological analysis of the positive inotropic effect of endothelin-1 in guinea pig left atria.

Endothelin-1 (ET-1) increased the force of contraction and stimulated phosphoinositide hydrolysis in guinea pig left atria. ET-1 at 20 nM produced a dual-component positive inotropic effect composed of an initial increasing phase (early component) and a second and late developing, greater positive inotropic phase (late component). The late component was preferentially and markedly inhibited by nifedipine and the protein kinase C inhibitors H-7 and staurosporine. In guinea pig left atria, the activation of protein kinase C might contribute to the establishment of the positive inotropic effect of ET-1 mediated by modulation of voltage-dependent Ca2+ channels.