Cardioprotection by KATP channels in wild-type hearts and hearts overexpressing A1 adenosine receptors

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Title Cardioprotection by KATP channels in wild-type hearts and hearts overexpressing A1 adenosine receptors
Author Headrick, John Patrick; Gauthier, NS.; Matherne, GP.
Journal Name American Journal of Physiology: Heart and Circulatory Physiology
Year Published 2000
Place of publication USA
Publisher American Physiological Society
Abstract We studied the role of mitochondrial ATP-sensitive K+(KATP) channels in modifying functional responses to 20 min global ischemia and 30 min reperfusion in wild-type mouse hearts and in hearts with ∼250-fold overexpression of functionally coupled A1-adenosine receptors (A1ARs). In wild-type hearts, time to onset of contracture (TOC) was 303 ± 24 s, with a peak contracture of 89 ± 5 mmHg. Diastolic pressure remained elevated at 52 ± 6 mmHg after reperfusion, and developed pressure recovered to 40 ± 6% of preischemia. A1AR overexpression markedly prolonged TOC to 517 ± 84 s, reduced contracture to 64 ± 6 mmHg, and improved recovery of diastolic (to 9 ± 4 mmHg) and developed pressure (to 82 ± 8%). 5-Hydroxydecanoate (5-HD; 100 μM), a mitochondrial KATPblocker, did not alter ischemic contracture in wild-type hearts, but increased diastolic pressure to 69 ± 8 mmHg and reduced developed pressure to 10 ± 5% during reperfusion. In transgenic hearts, 5-HD reduced TOC to 348 ± 18 s, increased postischemic contracture to 53 ± 4 mmHg, and reduced recovery of developed pressure to 22 ± 4%. In summary, these data are the first to demonstrate that endogenous activation of KATP channels improves tolerance to ischemia-reperfusion in murine myocardium. This functional protection occurs without modification of ischemic contracture. The data also support a role for mitochondrial KATP channel activation in the pronounced cardioprotection afforded by overexpression of myocardial A1ARs.
Peer Reviewed Yes
Published Yes
Publisher URI
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 279
Page from H1690
Page to H1697
ISSN 0363-6135
Date Accessioned 2001-01-01
Date Available 2015-02-05T03:42:49Z
Language en_US
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Subject PRE2009-Medical & Health Sciences
Publication Type Article in Scholarly Refereed Journal
Publication Type Code c1

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