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

Summary 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^–6–3×10^–6 M).The inotropic effect of dopamine was antagonized by practolol (3×10^–7–10^–6 M), but not by phentolamine (3×10^–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 (3×10^–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^–4–3×10^–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.