Comparison of the alpha adrenoceptor activity of dopamine, ibopamine and epinine in the pulmonary circulation of the dog.
The ability of dopamine, ibopamine and epinine to elicit alpha adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog. Animals were pretreated with propranolol to eliminate beta adrenoceptor-mediated relaxation of the pulmonary vasculature. Heparinized blood was withdrawn from the left femoral artery and transferred via a peristaltic pump to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung. The flow rate of the pump was adjusted so that mean pulmonary perfusion pressure in the lobe was equal to resting diastolic pulmonary artery pressure (10 +/- 1 mm Hg). Under conditions of constant left atrial pressure and pulmonary blood flow, intralobar administration of dopamine, ibopamine and epinine elicited dose-dependent increases in perfusion pressure of the lobe, reflecting increases in pulmonary vascular resistance. Prazosin (100 micrograms/kg i.v.), a selective alpha-1 adrenoceptor antagonist, inhibited the pulmonary vasopressor responses to dopamine, ibopamine and epinine. Rauwolscine (100 micrograms/kg i.v.), a selective alpha-2 adrenoceptor antagonist, inhibited pulmonary pressor responses to dopamine and epinine without altering significantly the pulmonary vasoconstrictor response to ibopamine. These data indicate that dopamine and epinine stimulate both postjunctional vascular alpha-1 and alpha-2 adrenoceptors to elicit pulmonary vasoconstriction in the dog, whereas ibopamine, when injected directly into the pulmonary circulation, stimulates primarily postjunctional vascular alpha-1 adrenoceptors. However, when ibopamine was administered intraduodenally, both prazosin and rauwolscine were found to inhibit the resulting pulmonary vasopressor response. This finding is consistent with the hypothesis that ibopamine is converted to its active metabolite epinine, which stimulates both pulmonary vascular alpha-1 and alpha-2 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003846:Deoxyepinephrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C023487:ibopamine; D011433:Propranolol; C015603:azepexole; D003846:Deoxyepinephrine; D004298:Dopamine; D011224:Prazosin