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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1875    most recent 00158.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Morrison, R. R. Articles by Mustafa, S. J. Search for Related Content PubMed PubMed Citation Articles by Morrison, R. R. Articles by Mustafa, S. J.

Effects of targeted deletion of A₁ adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes

¹Division of Critical Care Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee; ²Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia; ³Durham Research Center, University of Nebraska Medical Center, Omaha, Nebraska; ⁴Brody School of Medicine at East Carolina University, Greenville, North Carolina; and ⁵National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Submitted 16 February 2005 ; accepted in final form 2 May 2006

To examine ischemic tolerance in the absence of A₁ adenosine receptors (A₁ARs), isolated wild-type (WT) and A₁AR knockout (A₁KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A₁AR deletion and/or ischemia-reperfusion. A₁KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A₁AR deletion. After 20 min of ischemia, CF was attenuated in A₁KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A₁KO hearts (54.4 ± 5.1 vs. WT 81.1 ± 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A₁KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A₁AR transcript in A₁KO hearts, and the message for A_2A, A_2B, and A₃ adenosine receptors was similar in uninstrumented A₁KO and WT hearts. Ischemia-reperfusion increased A_2B mRNA expression 2.5-fold in both WT and A₁KO hearts without changing A₁ or A₃ expression. In WT hearts, ischemia transiently doubled A_2A mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A₁KO hearts. Together, these data affirm the cardioprotective role of A₁ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts.

gene expression; coronary flow; lactate dehydrogenase

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