Interaction of dopamine, (+/-)-dobutamine and the (-)-enantiomer of dobutamine with alpha- and beta-adrenoceptors in the pulmonary circulation of the dog.
The effects of dopamine, (+/-)-dobutamine (racemic mixture) and (-)-dobutamine on alpha-adrenoceptor-mediated vasoconstriction were evaluated in the pulmonary circulation of the anesthetized dog. The drugs were studied in the absence and presence of propranolol (1 mg/kg, i.v.) in order to assess beta-adrenoceptor-mediated effects in the pulmonary circulation. Intra-arterial administration of dopamine, (+/-)-dobutamine and (-)-dobutamine elicited dose-dependent increases in pulmonary perfusion pressure, reflecting increases in pulmonary vascular resistance. In control animals, dopamine elicited the largest increases in pulmonary perfusion pressure (45% above resting pulmonary pressure) followed by (-)-dobutamine (30% increase) and (+/-)-dobutamine (15% increase). The pressor effects of dopamine in the pulmonary circulation were mediated by both postjunctional vascular alpha 1- and alpha 2-adrenoceptors, since prazosin, (100 micrograms/kg, i.v.), a selective alpha 1-adrenoceptor antagonist, and rauwolscine (100 micrograms/kg, i.v.), a selective alpha 2-adrenoceptor antagonist, both inhibited the vasopressor response elicited by dopamine to roughly equivalent degrees. Pulmonary vasoconstriction produced by (+/-)-dobutamine and (-)-dobutamine was mediated primarily by postsynaptic vascular alpha 1-adrenoceptors, although alpha 2-adrenoceptor-mediated vasoconstriction was observed. In propranolol-pretreated animals, the increase in pulmonary perfusion pressure elicited by dopamine and (-)-dobutamine was qualitatively and quantitatively similar to that observed in control animals, suggesting that these agents have little activity on vascular beta 2-adrenoceptors in the pulmonary circulation. In marked contrast, the maximum pulmonary vasopressor response obtained with (+/-)-dobutamine were greater in propranolol-pretreated animals, indicating that (+/-)-dobutamine also has the capacity to stimulate pulmonary vascular beta 2-adrenoceptors which mediate pulmonary vasodilation that, in part, mask alpha-adrenoceptor-mediated pulmonary vasoconstriction. Since the (-)-enantiomer of dobutamine has little or no beta 2-adrenoceptor agonist activity, the beta 2-adrenoceptor-mediated effect of (+/-)-dobutamine must result from the (+)-enantiomer as has been previously proposed. The results of the present study indicate that dopamine has a greater propensity for increasing pulmonary vascular resistance, and therefore pulmonary arterial blood pressure, relative to (+/-)-dobutamine. This results, at least in part, from the relatively weaker activity of dopamine in stimulating pulmonary vascular beta 2-adrenoceptors which mediate vasodilation.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D004280:Dobutamine / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology*; D005260:Female; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013237:Stereoisomerism
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D004298:Dopamine