Evaluation of alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction in the in situ, autoperfused, pulmonary circulation of the anesthetized dog

RJ Shebuski, T Fujita and RR Ruffolo

Alpha-1 and alpha-2 adrenoceptor-mediated vasoconstriction was studied in the in situ, autoperfused pulmonary circulation of the open-chest anesthetized dog utilizing selective alpha adrenoceptor agonists and antagonists. Animals were pretreated with propranolol (1 mg/kg i.v.) to eliminate beta adrenoceptor-mediated effects in the pulmonary circulation. Blood was withdrawn from the right femoral artery and transferred, via a peristaltic pump, to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung.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 set so that the 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 alpha adrenoceptor agonists elicited increases in perfusion pressure of the lobe, reflecting changes in pulmonary vascular resistance. Intralobar administration of the selective alpha-1 adrenoceptor agonist methoxamine and the selective alpha-2 adrenoceptor agonist B-HT 933 elicited dose-dependent increases in lobar perfusion pressure, as did the nonselective alpha adrenoceptor agonist norepinephrine. Prazosin (100 micrograms/kg i.v.), a selective alpha-1 adrenoceptor antagonist, inhibited pulmonary vasopressor responses to methoxamine and norepinephrine without altering significantly the response to B-HT 933. Rauwolscine (100 micrograms/kg i.v.), a selective alpha-2 adrenoceptor antagonist, inhibited the response to B-HT 933 and norepinephrine with little effect on methoxamine. Intralobar administration of tyramine to evoke the release of endogenous norepinephrine resulted in dose-dependent increases in lobar perfusion pressure. The response to tyramine was inhibited selectively by prazosin with little effect of rauwolscine.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 238, Issue 1, pp. 217-223, 07/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics