Affiliation:
1. Department of Physiology and Pharmacology, Center for Interdisciplinary Research in Cardiovascular Sciences, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia;
2. Université Libre de Bruxelles, Brussels, Belgium; and
3. Bayer Health Care AG, Wuppertal, Germany
Abstract
Adenosine mediates vascular responses through four receptor subtypes: A1, A2A, A2B, and A3. The role of A2A receptors in aortic vascular tone was investigated using A2A adenosine receptor (AR) knockout (A2AKO) and corresponding wild-type (A2AWT) mice. Isolated aortic rings from A2AWT and A2AKO mice were precontracted with phenylephrine (10−7 M), and concentration responses for adenosine analogs and selective agonists/antagonists were obtained. Nonselective adenosine analog (NECA; EC50 = 6.78 μM) and CGS-21680 (A2AAR selective agonist; EC50 = 0.013 μM) produced concentration-dependent relaxation (maximum of 25% and 28% relaxation at 10−5 M NECA and CGS-21680, respectively) in A2AWT aorta. In A2AKO aorta, NECA (EC50 = 0.075 μM) induced concentration-dependent contraction (maximum contraction of 47% at 10−6 M; P < 0.05 compared with A2AWT), whereas CGS-21680 produced no response. SCH-58261 (10−6 M; A2AAR selective antagonist) abolished both NECA- and CGS-21680-mediated vasorelaxation in A2AWT ( P < 0.05), whereas no change was observed in A2AKO. When DPCPX (10−5 M; A1 selective antagonist) was used in NECA concentration response, greater vasorelaxation was observed in A2AWT (50% vs. 25% in controls at 10−5 M; P < 0.05), whereas lower contraction was seen in A2AKO tissues (5% vs. 47% in controls at 10−6 M; P < 0.05). Aortic endothelial function, determined by response to acetylcholine, was significantly higher in WT compared with KO (66% vs. 51%; P < 0.05). BAY 60–6583 (A2B selective agonist) produced similar relaxation in both KO and WT tissues. In conclusion, A2AAR KO mice had significantly lower aortic relaxation and endothelial function, suggesting that the A2AAR plays an important role in vasorelaxation, probably through an endothelium-dependent mechanism.
Publisher
American Physiological Society
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology
Cited by
42 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献