Does nitric oxide contribute to the negative chronotropic and inotropic effects of endothelin-1 in the heart?

Abstract

N ω -nitro- l-arginine methyl ester, an inhibitor of nitric oxide synthase, was used to examine whether nitric oxide was involved in the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian heart. In isolated rabbit right atria, endothelin-1 elicited a negative chronotropic effect in the presence of isoprenaline, which was associated with a decrease in the isoprenaline-induced accumulation of cyclic AMP. On the other hand, in the dog ventricular trabeculae, the negative inotropic effect of endothelin-1 was not accompanied by a significant reduction in the isoprenaline-induced accumulation of cyclic AMP. N ω -nitro- l-arginine methyl ester affected neither the negative chronotropic effect nor the negative inotropic effect of endothelin-1. The effects of endothelin-1 on the isoprenaline-induced cyclic AMP accumulation were not influenced by N ω -nitro- l-arginine methyl ester either. These results indicate that the negative chronotropic and inotropic effects of endothelin-1 in the presence of isoprenaline in mammalian cardiac muscle do not involve the nitric oxide-mediated signaling pathway.