Opposing effects of endothelin-1 on C-type natriuretic peptide actions in rat cardiomyocytes.
C-type natriuretic peptide (CNP) and Endothelin-1 are paracrine peptides with opposing vascular and mitogenic actions. In cardiac myocytes, CNP reduced contractility and induced accumulation of cyclic guanosine monophosphate (cGMP). Endothelin-1 caused an increase in contractile amplitude, abolished the negative inotropic effect of CNP, reduced the negative inotropic effect 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.
Fixler
R
R
Department of Cardiac Research Laboratory, Hadassah University Hospital, Jerusalem, Israel.
Hasin
Y
Y
Eilam
Y
Y
Zhang
D F
DF
Nir
A
A
D000818:Animals; D000831:Animals, Newborn; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D051381:Rats
D019332:Endothelin-1; D020098:Natriuretic Peptide, C-Type; D006152:Cyclic GMP