Effect of adenosine on pulmonary circulation of rabbits.
The effect and mechanism of action of adenosine on the pulmonary circulation of rabbits were studied. Adenosine (10(-5)-10(-3) M) produced a concentration-dependent decrease in pulmonary arterial tension of precontracted pulmonary arterial rings. Removal of endothelium (denuded) augmented the adenosine-induced vasodilation in the pulmonary arterial rings. Theophylline (5 x 10(-5) M), an adenosine receptor antagonist, reduces the vasodilation induced by adenosine in intact and denuded rings. Pretreatment of the pulmonary rings with the cyclooxygenase inhibitor indomethacin (5 x 10(-6) M) significantly attenuated the adenosine-induced relaxation in denuded but not in the intact pulmonary arterial rings. Methylene blue (5 x 10(-5) M), a guanylate cyclase inhibitor, significantly reduced the relaxation induced by adenosine in both the intact and the denuded arterial rings. Adenosine significantly attenuated the pressor responses of serotonin and acetylcholine in the intact and denuded rabbit's pulmonary arterial rings. The results of this study indicate that adenosine induces pulmonary vasodilation and that functional endothelium is not required to evoke this dilation. In addition, guanylate cyclase activity and the generation of cGMP is essential for adenosine 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.
El-Kashef
H
H
Department of Pharmacology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia. elkashef@ksu.edu.sa
Elmazar
M M
MM
Al-Shabanah
O A
OA
Al-Bekairi
A M
AM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D012701:Serotonin; D006162:Guanylate Cyclase; D000241:Adenosine