Adenosine A1 and A2 receptors mediate tone-dependent responses in feline pulmonary vascular bed
Cheng, D.Y.; DeWitt, B.J.; Suzuki, F.; Neely, C.F.; Kadowitz, P.J.
American Journal of Physiology 270(1 Pt 2): H200-H207
1996
ISSN/ISBN: 0002-9513 PMID: 8769752 Document Number: 462529
Adenosine produces tone-dependent pulmonary vascular responses; however, the adenosine receptor subtype mediating these responses is unknown. In the present study, the adenosine receptor subtypes mediating tone-dependent responses were investigated. Intralobar injections of adenosine, ATP, and analogues under low-tone conditions caused dose-related increases in lobar arterial pressure; the order of potency was alpha,beta-methylene ATP (alpha,beta-metATP) gt N-6-cyclopentyladenosine (CPA) gt ATP gt adenosine. Under low-tone conditions, pressor responses to adenosine, ATP, and CPA, an adenosine A-1-receptor agonist, were reduced by KW-3902, an adenosine A-1-receptor antagonist, whereas KW-3902 and meclofenamate had no effect on responses to alpha,beta-metATP, norepinephrine, serotonin, or angiotensin II. Under elevated-tone conditions, injections of adenosine, ATP, and analogues caused dose-related decreases in lobar arterial pressure, and adenosine was 10-fold less potent than 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A-2-receptor agonist, and ATP. KF17837, an A-2-receptor antagonist, reduced vasodilator responses to adenosine and CPCA, whereas responses to ATP, isoproterenol, diethylamine-NO, lemakalim, and bradykinin were not changed. The vasodilator responses to adenosine were not attenuated by N-omega-nitro-L-arginine benzyl ester, methylene blue, or U-37883A. These results suggest that vasoconstrictor responses to adenosine are mediated by A-1 receptors and the release of vasoconstrictor prostanoids, and that, under elevated-tone conditions, vasodilator responses are mediated by A-2 receptors but not the release of nitric oxide or the activation of guanylate cyclase or K-ATP+ channels.