ROLE OF NITRIC-OXIDE IN ADENOSINE RECEPTOR-MEDIATED RELAXATION OF PORCINE CORONARY-ARTERY

In the present study, using porcine coronary artery rings in vitro, we examined the role of the nitric oxide (NO) pathway in endothelium-dep endent vasorelaxant effects of the 5'-uronamide adenosine agonists, 5' -(N-ethylcarboxamido)adenosine (NECA) and )]phenylethyl-amino-5'-N-eth ylcarboxamidoadenosine (CGS-21680) as opposed to the endothelium-indep endent actions of the C2- and N-6-substituted analogues, 2-chloroadeno sine (CAD) and N-6-cyclopentyladenosine (CPA). The NO synthase inhibit or, N-G-monomethyl-L-arginine (L-NMMA, 30 mu M), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 mu M), attenuated t he relaxations of endothelium-intact but not -denuded rings to NECA an d CGS-21680. The effect of L-NMMA on NECA-induced relaxation was rever sed by L-arginine (100 mu M), a substrate for NO synthesis. In the end othelium-intact tissues, both NECA and CGS-21680 elicited enhanced pro duction of nitrite, a stable metabolite of NO. This was also attenuate d by L-NMMA or endothelium removal. Furthermore, NECA (10 mu M) induce d augmentation of guanosine 3',5'-cyclic monophosphate (cGMP) producti on in the intact arteries, which was also inhibited by L-NMMA, LY-8358 3, or endothelium removal. In contrast, vasorelaxant responses generat ed 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 guanosine 3' , 5'-cyclic monophosphate (cGMP) levels of the coronary artery. The da ta suggest that endothelium-dependent relaxations of porcine coronary artery evoked by the 5'-uronamide adenosine agonists, NECA and CGS-216 80, involve the release of NO from the endothelium, and cGMP appears t o be a mediator for this effect.