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Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury

Maddock, HL; Mocanu, MM; Yellon, DM; (2002) Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury. AM J PHYSIOL-HEART C , 283 (4) H1307 - H1313. 10.1152/ajpheart.00851.2001.

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Abstract

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 are unclear. We therefore studied the role of the A(3) receptor (A(3)R) in ameliorating RI using the specific A3R agonist 1-[2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxi-N-methyl-b-D-ribofuranuronamide (2-Cl-IB-MECA). Isolated rat hearts and cardiomyocytes were subjected to ischemia or simulated ischemia, followed by reperfusion/reoxygenation. The end points were percent 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 0.1 nM, P < 0.05). In isolated myocytes, apoptosis and necrosis were significantly reduced compared with controls (5.7 +/- 2.6% vs. 17.1 +/- 1.3% and 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 A(2a) receptor activation was also examined. This is the first study to demonstrate that A(3)R activation at reperfusion limits myocardial injury in the isolated rat heart and improves survival in isolated myocytes, possibly by antiapoptotic and antinecrotic mechanisms.

Type:Article
Title:Adenosine A(3) receptor activation protects the myocardium from reperfusion/reoxygenation injury
DOI:10.1152/ajpheart.00851.2001
Keywords:reperfusion injury, necrosis, apoptosis, REPERFUSION INJURY, CARDIAC MYOCYTES, INFARCT SIZE, INTRAVENOUS ADENOSINE, SIMULATED ISCHEMIA, MAST-CELLS, KINASE-B, APOPTOSIS, A(1), HEART
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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