Effects of dopamine on sinus rate and ventricular contractile force of the dog heart in vitro and in vivo.

1 Experiments were carried out on dog isolated papillary muscle and sinus node preparations perfused with arterial blood from a donor dog. The chronotropic and inotropic effects of dopamine were analysed by using reserpine, desmethylimipramine (DMI), cocaine and phenoxybenzamine, and the relative chronotropic and inotropic effects defined, the results being compared with those for noradrenaline (NA). 2 The effects of dopamine administered intra-arterially into the isolated preparations were reduced by pretreatment of animals with reserpine both in the papillary muscle and sinus node. The chronotropic effects, however, were affected less by pretreatment with reserpine than were the inotropic effects. 3 Desmethylimipramine (DMI) reduced the inotropic and chronotropic effects of dopamine, and enhanced the effects of NA and nerve stimulation; the chronotropic effects of the amines were less affected than the inotropic effects. 4 Cocaine enhanced considerably the inotropic and chronotropic effects of NA, and decreased the inotropic but not the chronotropic effect of dopamine. 5 Phenoxybenzamine enhanced the inotropic effects of dopamine, NA and nerve stimulation, but did not affect the chronotropic effects of the amines. 6 When dopamine (1 to 300 mug/kg) was administered intravenously to the donor dog, it increased preferentially the contractile force of the ventricular myocardium with a comparatively small change of the sinus rate in the isolated preparations as well as in the heart in vivo. NA (0.1 to 10 mug/kg) caused effects similar to those of dopamine. The maximal inotropic responses to these catecholamines were reached with lower doses than the chronotropic ones. 7 It is concluded that both the positive inotropic and the positive chronotropic responses to dopamine are mediated partially by a direct and partially by an indirect stimulant effect on beta-adrenoceptors in the dog heart. The present results suggest that the difference in activity of dopamine and NA between the ventricular myocardium and the sinus node may be ascribed to the unequal innervation with adrenergic nerve fibres of the atrium and the ventricle (Furnival, Linden & Snow, 1971). The sinus node which is densely innervated by adrenergic nerve fibres may inactivate noradrenaline and dopamine more effectively than the ventricular myocardium through the uptake into the nerve and thereby be less sensitive to the exogenous catecholamines.