Presynaptic dopamine receptors and alpha-adrenoceptors as mediators of the bradycardic action of N-n-propyl-N-n-butyl dopamine.
The role of presynaptic receptors in the bradycardic action of N-n-butyl dopamine (PBDA) was investigated. A biphasic effect on blood pressure and a decrease in heart rate were seen upon intravenous administration of PBDA to pentobarbital-anesthetized dogs. The bradycardia produced by PBDA was unaffected by bilateral vagotomy; however, it was abolished by cardiac sympathetic denervation. When PBDA was readministered following restoration of the cardiac sympathetic nerve activity by electrical stimulation, at frequency of 1 Hz, decrease in heart rate was again observed. The cardioinhibitory action of PBDA was completely abolished by sulpiride, whereas phentolamine and yohimbine caused only partial attenuation, suggesting the involvement of both presynaptic alpha-adrenoceptors as well as dopamine receptors in the bradycardiac action of PBDA. Additional experiments were performed to study the influence of stimulus frequency on the cardioinhibition produced by PBDA. Administration of PBDA to animals with different levels of cardiac sympathetic nerve activity (0.25-2 Hz) resulted in decreases in heart rate. However, yohimbine antagonized this action of PBDA only at the two higher frequencies of cardiac nerve stimulation. Sulpiride completely abolished the bradycardia observed at all the different frequencies of cardiac nerve stimulation. These results demonstrate that activation of presynaptic receptors on cardiac sympathetic nerves can result in a decrease in heart rate. PBDA causes bradycardia via an action on presynaptic dopamine receptors when the cardiac sympathetic nerve activity is low, while both presynaptic dopamine receptors as well as alpha-adrenoceptors are involved in the decrease in heart rate produced by this compound at higher levels of sympathetic nerve activity.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D008297:Male; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D002317:Cardiovascular Agents; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; C016080:N-n-propyl-N-n-butyl-beta-dopamine; D004298:Dopamine