Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxigenation injury

doi:10.1152/ajpheart.00851.2001

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Adenosine A3 receptor activation protects the myocardium from reperfusion/reoxigenation injury

Helen L Maddock¹, Mihaela M Mocanu¹^*, and Derek M Yellon¹

¹ Cardiology, The Hatter Institute, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: m.mocanu{at}ucl.ac.uk.

Ischemia/reperfusion induces both necrotic and apoptotic cell death. The ability of adenosine to attenuate reperfusion-induced injury (RI) and the role played by adenosine receptors is unclear. We therefore studied the role of the A3 receptor (A3R) in ameliorating RI using the specific A3R agonist 2-Cl-IB-MECA. Isolated rat heart and cardiomyocytes were subjected to ischemia or simulated ischemia followed by reperfusion/reoxygenation. The end-points were % infarction/risk zone and annexin-V (apoptosis) and/or propidium iodide positivity (necrosis) respectively. In isolated hearts 2-Cl-IB-MECA significantly limited infarct size (44.2±2.7% in control vs. 21.9±2.4%, at 1 nM and 35.8±3.3%, at 0.1nM, p<0.05). In isolated myocytes apoptosis and necrosis were significantly reduced compared to control (5.7±2.6% vs. 17.1±1.3%, 13.7±2.0% vs. 23.1±1.5%, respectively, p<0.0001). In both models the beneficial effects were abrogated using the A3R antagonist MRS-1191. The involvement of the A2a receptor activation was also examined. This is the first study to demonstrate that A3R activation at reperfusion limits myocardial injury in isolated rat heart and improves survival in isolated myocytes, possibly by anti-apoptotic and anti-necrotic mechanisms.

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