The mode of direct action of dopamine on the rabbit heart

The effects of dopamine on the force of contraction and on cylic adenosine monophosphate (AMP) levels were investigated in isolated electrically driven left atria (32 degrees C, 1 Hz) and papillary muscles (37 degrees C, 0.5 Hz) of the rabbit. In both preparations only the combined application of phentolamine (10(-6) M) and pindolol (3 X 10(-8) M) shifted the entire dose-response curves for the positive inotropic effect of dopamine to the right, while either antagonist used separately had no effect. Similar results were obtained when the indirect action of dopamine via the release of endogenous noradrenaline was inhibited by cocaine (3 X 10(-5) M) or by pretreatment of the rabbits with reserpine (6 mg/kg, s.c., 16 hr). Increases in cyclic AMP induced by dopamine (10(-4) M in atria and 3 X 10(-4) M in papillary muscles) were prevented by cocaine or by pretreatment with reserpine, indicating that these increases are mainly evoked by released endogenous noradrenaline. It is concluded that both alpha- and beta- adrenoceptors may play roles in the direct positive inotropic action of dopamine in the rabbit heart. The failure of the direct action of dopamine to increase cyclic AMP may be due to a cyclic-AMP-decreasing effect of alpha-adrenoceptor stimulation, which may counteract cyclic AMP increases induced by dopamine via beta-adrenoceptor stimulation.