Inotropic effects of endothelin on mammalian ventricular contractility

Endothelin-1 elicited a concentration-dependent positive inotropic effect on the isolated rabbit, guinea pig, and rat, but not on the dog ventricular myocardium. The duration of isometric contractions was prolonged by endothelin-1 in a concentration-dependent manner, mainly by prolongation of relaxation time. Phorbol 12,13-dibutyrate (PDBu) (a tumor-promoting phorbol ester) inhibited the positive inotropic effect of endothelin-1, as well as myocardial alpha 1-adrenoceptor stimulation at low concentrations (10(-9) mol/l and above) without (10(-8) mol/l) or less (10(-7) mol/l) affecting the basal force of contraction, and the positive inotropic effect of beta-adrenoceptor stimulation. The present findings indicate that endothelin elicits a positive inotropic effect on mammalian ventricular myocardium, the characteristics of which are very similar to those of myocardial alpha-adrenoceptor stimulation.