ADENOSINE A(1) AND A(2) RECEPTORS MEDIATE TONE-DEPENDENT RESPONSES INFELINE PULMONARY VASCULAR BED

Adenosine produces tone-dependent pulmonary vascular responses; howeve r, 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 adeno sine, 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) > N-6-cyclopentyladenosine (CPA ) > ATP > adenosine. Under low-tone conditions, presser responses to a denosine, ATP, and CPA, an adenosine A(1)-receptor agonist, were reduc ed by KW-3902, an adenosine A(1)-receptor antagonist, whereas KW-3902 and meclofenamate had no effect on responses to alpha,beta-metATP, nor epinephrine, serotonin, or angiotensin II. Under elevated-tone conditi ons, injections of adenosine, ATP, and analogues caused dose-related d ecreases in lobar arterial pressure, and adenosine was 10-fold less po tent than 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A(2)-rece ptor agonist, and ATP. KF-17837, an A(2)-receptor antagonist, reduced vasodilator responses to adenosine and CPCA, whereas responses to ATP, isoproterenol, diethylamine-NO, lemakalim, and bradykinin were not ch anged. The vasodilator responses to adenosine were not attenuated by N -omega-nitro-L-arginine benzyl ester, methylene blue, or U-37883A. The se results suggest that vasoconstrictor responses to adenosine are med iated 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.