Role of nitric oxide in adenosine receptor-mediated relaxation of porcine coronary artery. Abebe, Worku, Tahir Hussain, Hammed Olanrewaju, and S. Jamal Mustafa. Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4354, U.S.A.
APStracts 2:0230H, 1995.
In the present study, using porcine coronary artery rings in vitro, we examined the role of the nitric oxide pathway in endothelium -dependent vasorelaxant effects of the 5'-uronamide adenosine agonists, 5'-(N-ethylcarboxamido)adenosine (NECA) and 2-[p-(2 -carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS -21680) as opposed to the endothelium-independent actions of the C2- and N6-substituted analogs, 2-chloroadenosine (CAD), and N6 -cyclopentyladenosine (CPA). The nitric oxide synthase inhibitor, N6 -monomethyl- L-arginine (L-NMMA, 30 [mu]M), and the nitric oxide destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 [mu]M), attenuated the relaxations of endothelium-intact but not denuded rings to NECA and CGS-21680. The effect of L-NMMA on NECA-induced relaxation was reversed by L-arginine (100 [mu]M), a substrate for nitric oxide synthesis. In the endothelium-intact tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a stable metabolite of nitric oxide. This was also attenuated by L-NMMA or endothelium removal. Furthermore, NECA (10 [mu]M) induced augmentation of cGMP production in the intact arteries, which was also inhibited by L-NMMA, LY-83583 or endothelium removal. In contrast, vasorelaxant responses generated by CAD and CPA were not altered by either L-NMMA or LY-83583. Both agents (10 [mu]M) were also unable to alter nitrite and / or cGMP levels of the coronary artery. The data suggest that endothelium-dependent relaxations of porcine coronary artery evoked by the 5'-uronamide adenosine agonists, NECA and CGS-21680, involve the release of nitric oxide from the endothelium, and cGMP appears to be a mediator for this effect. 

Received 16 December 1994; accepted in final form 26 May 1995.
APS Manuscript Number H1103-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  8 June 1995.