Author:
Ansari Habib R.,Nadeem Ahmed,Talukder M. A. Hassan,Sakhalkar Shilpa,Mustafa S. Jamal
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 A2B-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.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
60 articles.
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