Role of nitric oxide in adenosine receptor-mediated relaxation of porcine coronary artery

W. Abebe, T. Hussain, H. Olanrewaju, S. J. Mustafa

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Abstract

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, N(G)-monomethyl-L-arginine (L-NMMA, 30 μM), and the NO-destroying agent, 6-anilino-5,8-quinolinedione (LY-83583, 10 μM), 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 μM), 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 μM) 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 μM) were also unable to alter nitrite and/or guanosine 3',5'-cyclic monophosphate (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 NO from the endothelium, and cGMP appears to be a mediator for this effect.

Original languageEnglish (US)
Pages (from-to)H1672-H1678
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number5 38-5
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • 2- chloroadenosine
  • 2-[p(2- carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosine
  • 5'(N-ethylcarboxamido)adenosine
  • 6-anilino-5,8-quinolinedione
  • N(G)-monomethyl-L- arginine
  • N-cyclopentyladenosine
  • endothelium
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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