The effect and mechanism of action of adenosine on the pulmonary circulatio
n of rabbits were studied. Adenosine (10(-5)-10(-3) M) produced a concentra
tion-dependent decrease in pulmonary arterial tension; of precontracted pul
monary arterial rings. Removal of endothelium (denuded) augmented the adeno
sine-induced vasodilation in the pulmonary arterial rings. Theophylline (5
x 10(-5) M), an adenosine receptor antagonist, reduces the vasodilation ind
uced by adenosine in intact and denuded rings. Pretreatment of the pulmonar
y rings with the cyclooxygenase inhibitor indomethacin (5 x 10(-6) M) signi
ficantly attenuated the adenosine-induced relaxation in denuded but not in
the intact pulmonary arterial rings. Methylene blue (5 x 10(-5) M), a guany
late cyclase inhibitor, significantly reduced the relaxation induced by ade
nosine in both the intact and the denuded arterial rings. Adenosine signifi
cantly attenuated the presser responses of serotonin and acetylcholine in t
he intact and denuded rabbit's pulmonary arterial rings. The results of thi
s study indicate that adenosine induces pulmonary vasodilation and that fun
ctional endothelium is not required to evoke this dilation. In addition, gu
anylate cyclase activity and the generation of cGMP is essential for adenos
ine to induce vasodilation in the rabbit lung. Furthermore, the results of
this study may suggest that adenosine could be used to reduce the severity
of pulmonary hypertension and possibly pulmonary edema. (C) 1999 Elsevier S
cience Inc. All rights reserved.