Dy. Cheng et al., ADENOSINE A(1) AND A(2) RECEPTORS MEDIATE TONE-DEPENDENT RESPONSES INFELINE PULMONARY VASCULAR BED, American journal of physiology. Heart and circulatory physiology, 39(1), 1996, pp. 200-207
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.