Studies on the positive inotropic effect of dopamine in the guinea-pig heart.

The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.