α- and β-adrenoceptors but not Dopaminergic Receptors are Involved in the Positive Inotropic Action of Dopamine in the Rabbit Heart

Abstract

On isolated electrically driven left atria (32°C, 1 Hz) and papillary muscles (37°C, 0.5 Hz) of the rabbit the mechanism underlying the positive inotropic action of dopamine was investigated. On both preparations the dose-response curve for dopamine was not influenced by phentolamine (10−6M) or pindolol (3×10−8M), when these agents were given separately. The specific dopaminergic receptor antagonists haloperidol (10−6 and 3×10−6M), pimozide (10−6 and 3×10−6M) and bulbocapnine (10−5M) did also not significantly modify the dose-response curve for dopamine. Only in the presence of phentolamine plus pindolol the entire curve was displaced to the right in a parallel manner by about 1.0 log unit. In contrast to dopamine epinine caused its positive inotropic effect on the papillary muscle in a concentration-dependent manner: its effect in lower concentrations was antagonized by phentolamine, while that of higher concentrations was inhibited by pindolol. 10−4M dopamine increased on both preparations cyclic AMP by about 50% after 60 s; this increase was not influenced by the dopaminergic receptor antagonists, but completely abolished by pindolol. It is concluded that dopamine produces its positive inotropic effect on the rabbit heart through a cyclic AMP dependent β-adrenoceptor stimulation as well as through an α-adrenoceptor stimulation to about the same degree. Stimulation of receptors specific to dopamine, however, seems not to be involved.