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-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 analogues, 2-chloroadenosine (CAD) and N6-cyclopentyladenosine (CPA). The NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 30 microM), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 microM), 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 microM), a substrate for NO synthesis. In the endothelium-intact tissues, both NECA and CGS-21680 elicited enhanced production of nitrite, a stable metabolite of NO. This was also attenuated by L-NMMA or endothelium removal. Furthermore, NECA (10 microM) induced augmentation of guanosine 3',5'-cyclic monophosphate (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 microM) were also unable to alter nitrite and/or guanosine 3',5'-cyclic monophosphate (cGMP) levels of the coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Abebe
W
W
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354, USA.
Hussain
T
T
Olanrewaju
H
H
Mustafa
S J
SJ
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000096:biosynthesis; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine
D000634:Aminoquinolines; D009573:Nitrites; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006152:Cyclic GMP