Comparison of the effects of dobutamine with dopamine and isoproterenol on inotropism and chronotropism in the mammalian heart

Abstract

The effects of dobutamine on inotropism and chronotropism of the heart were studied in vivo and in vitro and were compared with those of dopamine and isoproterenol. These compounds increased epicardial contractile force and the heart rate of the open-chest, bilaterally vagotomized dog under pentobarbital anesthesia. The dose-ratio for the contraction was [dobutamine: dopamine: isoproterenol 1:0.8:40] and for the heart rate, [=1:1:300]. Both drugs augmented the twitch contraction of the isolated dog ventricular papillary muscle with the dose-ratio of [dobutamine: dopamine: isoproterenol=1:0.7:11]. This mechanical response was associated with an elevation of the plateau voltage and an increase in repolarization of the action potential, but with no alteration of the maximum rate of rise of the action potential, the resting potential and the input membrane resistance. The discharge frequency of the rabbit S-A node pacemaker potential was accelerated chiefly due to an increase in the slope of the diastolic slow depolarization. With concentration of these catecholamines for the equivalent positive inotropic potency on the papillary muscle, this effect of isoproterenol was more potent than the effects of dobutamine and dopamine. These positive inotropic and chronotropic actions of the catecholamines were abolished by a β-receptor antagonist. Those actions of dopamine were markedly reduced by reserpine pretreatment. In addition, dobutamine had little vascular effect. These results indicate that dobutamine has a positive inotropic effect and a less positive chronotropic effect and that such is due to the direct action on the ventricular myocardium and the S-A node through β1-adrenergic receptors. © 1979, The Japanese Pharmacological Society. All rights reserved.