Evidence for the involvement of nitric oxide in A2B receptor-mediated vasorelaxation of mouse aorta

Habib R. Ansari, Ahmed Nadeem, M. A.Hassan Talukder, Shilpa Sakhalkar, S. Jamal Mustafa

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51 Scopus citations

Abstract

We have investigated the role of adenosine and its analogs on vasorelaxation of mouse aorta in intact endothelium with rank order of potency as follows: 5′-N-ethylcarboxamidoadenosine (NECA) > 2-chloroadenosine > adenosine > CGS-21680, which is consistent with the profile of A 2B-adenosine receptor (A2BAR). In endothelium-intact tissues, acetylcholine produced relaxation ranging from 65 to 80% in phenylephrine (PE, 10-7 M)-precontracted mouse aorta, whereas no relaxation was observed in endothelium-denuded tissues. The A2BAR antagonist alloxazine (10-5 M) shifted concentration-response curve for NECA (EC50 = 0.005 × 10-5 M) to the right with an EC50 of 2.8 × 10-5 M, demonstrating that this relaxation is partially dependent on functional endothelium mediated predominantly via A2BAR in this tissue. This conclusion was further supported by the following findings: 1) in the endothelium-intact mouse aorta, the EC50 values for NECA and adenosine were found to be 0.05 and 1.99 × 10-4 M, respectively; however, in denuded endothelium, these values were 0.098 and 3.55 × 10-4 M, respectively; 2) NECA-induced relaxation was significantly blocked by NG-nitro-L- arginine methyl ester (L-NAME; 10-4 M) in endothelium-intact tissues, which was reversed by pretreatment with L-arginine (10-4 M), whereas no significant inhibition was found in endothelium-denuded tissues; 3) total nitrites and nitrates (NOx) in intact endothelium with L-NAME (10-4 M) alone and in combination with L-arginine were 59% (P < 0.05) and 96%, respectively, in comparison with control (PE + NECA); and 4) endothelial nitric oxide synthase gene expression was found to be 67% (P < 0.05) less in endothelium-denuded as opposed to endothelium-intact mouse aorta. Thus these data demonstrate that adenosine-mediated vasorelaxation is partially dependent on A2BAR in mouse aorta.

Original languageEnglish (US)
Pages (from-to)H719-H725
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 2007

All Science Journal Classification (ASJC) codes

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

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