Opposing effects of endothelin-1 on C-type natriuretic peptide actions in rat cardiomyocytes

C-type natriuretic peptide (CNP) and Endothelin-l are paracrine peptides wi th opposing vascular and mitogenic actions. In cardiac myocytrs, CNP reduce d contractility and induced accumulation of cyclic guanosine monophosphate (cGMP). Endothelin-l caused an increase in contractile amplitude, abolished the negative inotropic effect of CNP, reduced the negative inotropic effec t of a membrane permeable cGMP, and inhibited cGMP accumulation induced by CNP. We conclude that endothelin-1 abolishes the negative inotropic effect of CNP. This effect may be mediated by inhibition of the negative inotropic actions of cGMP as well as by reduction of cGMP levels. (C) 2001 Elsevier Science B.V. All rights reserved.