A Possible Mode of Cardiovascular Actions of Dopamine in Dogs

Abstract

Abstract-A possible mode of cardiovascular actions of dopamine was studied using ephedrine. In the dog pretreated with repeated administrations of ephedrine (total dose, 40 or 80 mg/kg, i.v.) or with combined administrations of ephedrine (total dose, 90 mg/ kg, s.c. and i.v.) and reserpine (2 mg/kg, s.c., 24 hr previously), pressor responses to dopamine were eliminated and reversed to depressor responses whereas depressor responses to dopamine were potentiated.Positive chronotropic effects of dopamine were almost eliminated. Pressor and positive chronotropic effects of tyramine were almost abolished.Sympathomimetic effect of noradrenaline and adrenaline were potentiated while those of isoprenaline were inhibited. In the heart-lung preparation of ephedrine-treated dogs (total dose, 40 mg/kg, i.v.), cardiac stimulating effects of dopamine and tyrarnine were strongly depressed, and those of noradrenaline, adrenaline and isoprenaline were reduced to some extent. In the open-chest dogs, after pretreatment with cocaine (4 mg/kg, i.v.), pressor, positive inotropic and chronotropic effects of noradrenaline were potentiated whilst those of tyramine were inhibited. Those of dopamine were not visibly altered, but depressor, negative chronotropic and inotropic effects of dopamine appeared at small doses. In the ephedrine-pretreated dogs, these sympathomimetic effects of dopamine and tyramine after cocaine were strongly de pressed and those of noradrenaline were inhibited to a certain degree. The results obtained with ephedrine suggest that dopamine differs from other catecholamines and tyramine in the mode of cardiovascular actions.Studies have shown that sympathomimetic agents can be classified in their mode of action as acting directly on the receptors, acting indirectly on the adrenergic nerve terminals and those with mixed action, these classifications being principally based on the modifications in the effects after pretreatment by chronic denervation, cocaine or reserpine (1). Concerning dopamine, other workers reported modifications in responses to dopamine by denervation or cocaine led to classification of dopamine as a directly-acting amine (2-4). As results in the reserpine-pretreated animals are considered to be of importance in order to confirm the concept of direct and indirect effect, dopamine, although it has direct sympathomimetic actions, does to some extent act indirectly (5, 6). Farmer (7) reported that the pressor effect of dopamine was slightly potentiated while the positive chronotropic effect was reduced slightly 24 hr after reserpine in the cat. We have already observed that the pressor response to dopamine was potentiated 24 hr after pretreatment with reserpine (8), whereas the re This work was funded by grants from the Ministry of Education, Japan, and from the Kanae Foundation for Medical Research