Effect of modulating cardiac A1 adenosine receptor expression on protection with ischemic preconditioning

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Title Effect of modulating cardiac A1 adenosine receptor expression on protection with ischemic preconditioning
Author Lankford, Amy R; Yang, Jing Ning; Rose'Meyer, Roselyn Barbara; French, Brent A; Matherne, G Paul; Fredholm, Bertil B; Yang, Zequan
Journal Name American Journal of Physiology (Heart and Circulatory Physiology
Year Published 2006
Place of publication Rockville Pike, Bethesda, MD, USA
Publisher American Physiology Society
Abstract Activation of A1 adenosine receptors (A1ARs) may be a crucial step in protection against myocardial ischemia-reperfusion (I/R) injury; however, the use of pharmacological A1AR antagonists to inhibit myocardial protection has yielded inconclusive results. In the current study, we have used mice with genetically modified A1AR expression to define the role of A1AR in intrinsic protection and ischemic preconditioning (IPC) against I/R injury. Normal wild-type (WT) mice, knockout mice with deleted (A1KO−/−) or single-copy (A1KO+/−) A1AR, and transgenic mice (A1TG) with increased cardiac A1AR expression underwent 45 min of left anterior descending coronary artery occlusion, followed by 60 min of reperfusion. Subsets of each group were preconditioned with short durations of ischemia (3 cycles of 5 min of occlusion and 5 min of reperfusion) before index ischemia. Infarct size (IF) in WT, A1KO+/−, and A1KO−/− mice was (in % of risk region) 58 ± 3, 60 ± 4, and 61 ± 2, respectively, and was less in A1TG mice (39 ± 4, P < 0.05). A strong correlation was observed between A1AR expression level and response to IPC. IF was significantly reduced by IPC in WT mice (35 ± 3, P < 0.05 vs. WT), A1KO+/− + IPC (48 ± 4, P < 0.05 vs. A1KO+/−), and A1TG + IPC mice (24 ± 2, P < 0.05 vs. A1TG). However, IPC did not decrease IF in A1KO−/− + IPC mice (63 ± 2). In addition, A1KO−/− hearts subjected to global I/R injury demonstrated diminished recovery of developed pressure and diastolic function compared with WT controls. These findings demonstrate that A1ARs are critical for protection from myocardial I/R injury and that cardioprotection with IPC is relative to the level of A1AR gene expression.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1152/ajpheart.00181.2005
Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Volume 290
Page from 1469
Page to 1473
ISSN 0363-6135
Date Accessioned 2007-03-21
Date Available 2015-02-04T04:26:08Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Basic Pharmacology
URI http://hdl.handle.net/10072/14103
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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