Adenosine does not mediate the pulmonary vasodilator response of adenosine 5'-triphosphate in the feline pulmonary vascular bed

CF Neely, PJ Kadowitz, H Lippton, M Neiman and AL Hyman

Department of Anesthesia, Tulane University School of Medicine, New Orleans, Louisiana.

Adenosine and ATP produce dose- and tone-dependent responses in the feline pulmonary vascular bed. That is, at baseline (low) pulmonary vascular tone adenosine and ATP produce vasoconstrictor responses and at elevated pulmonary vascular tone adenosine and ATP produce vasodilator responses. The mechanism mediating the vasodilator responses to adenosine and ATP was investigated in the intact-chest cat under conditions of controlled pulmonary blood flow and left atrial pressure. When lobar vascular resistance was raised with U46619, intralobar injections of adenosine and ATP caused dose-related decreases in lobar arterial pressure. The pulmonary vasodilator responses to ATP and adenosine were not altered by atropine, propranolol, meclofenamate or cimetidine indicating that these responses were not mediated by the release of vasodilator prostaglandins or to activation of beta adrenergic, muscarinic or histamine (H2) receptors. The decreases in lobar arterial pressure in response to adenosine were reduced significantly by BWA1433U, an adenosine (P1) receptor antagonist. BWA1433U induced a parallel shift of the adenosine dose-response curve to the right; however, it had no significant inhibitory effect on the decrease in lobar arterial pressure in response to ATP. The P1 receptor antagonist in doses of 10 and 30 mg/kg i.v. had no significant effect on the vasodilator response to nitroglycerin. The present data suggest that vasodilator responses to adenosine in the feline pulmonary vascular bed are mediated by adenosine (P1) receptors, whereas responses to ATP are mediated by a different mechanism that does not involve release of a vasodilator prostaglandin.

Volume 250, Issue 1, pp. 170-176, 07/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics

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