Intrinsic and extrinsic P2 purinoceptor-mediated cardioprotection in mice

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Title Intrinsic and extrinsic P2 purinoceptor-mediated cardioprotection in mice
Author Wee, Shirley; Headrick, John P.; Peart, Jason N.
Journal Name Journal of Molecular and Cellular Cardiology
Editor Dr. R. A. Walsh (Editor-in-Chief)
Year Published 2007
Place of publication United Kingdom
Publisher Academic Press
Abstract P2 purinoceptor-dependent control of resistance to ischemia reperfusion injuries was studied in Langendorff perfused C57/Bl6 mouse hearts subjected to 20 min ischemia and 45 min reperfusion. Effects of P2 agonism and antagonism were assessed. Control hearts recovered 68 ± 4 mm Hg ventricular pressure (63 ± 3% pre-ischaemia), exhibited sustained diastolic contracture (23 ± 2 mm Hg), and released 26 ± 4 U/g lactate dehydrogenase (LDH) during reperfusion, evidencing oncosis. Treatment with 250 nM of the P2 agonist uridine 5′-triphosphate (UTP) for 10 min prior to and 10 min after ischemia reduced diastolic contracture by not, vert, similar 50% (9 ± 2 mm Hg), improved pressure development (85 ± 5 mm Hg; 77 ± 2% of baseline), and reduced LDH loss by 60% (11 ± 2 U/g). In contrast, P2Y1 agonism with 50 nM 2-methyl-thio-ATP was ineffective. P2 antagonism with 200 μM suramin impaired post-ischemic outcomes, exaggerating contractile dysfunction (41 ± 2 mm Hg diastolic pressure; 33 ± 5 mm Hg developed pressure) and LDH loss (53 ± 9 U/g). In the presence of suramin, UTP no longer modified post-ischemic function or oncosis. Evidence of intrinsic P2-mediated protection is consistent with ischemic elevations in microdialysate [UTP], [ATP] and [ADP]. In summary, these data evidence myocardial protection via endogenous and exogenous P2 agonists: enhanced recoveries with UTP, together with exaggeration of intrinsic injury and inhibition of UTP-protection with suramin, support protection via exogenously and intrinsically activated P2 purinoceptors. Data implicate P2Y2 receptors in cardioprotection, though further work is required to identify the sub-type involved.
Peer Reviewed No
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.yjmcc.2007.03.572
Volume 42
Issue Number 6 Supp1
Page from S187
Page to S187
ISSN 0022-2828
Date Accessioned 2009-04-06
Date Available 2010-02-24T06:26:24Z
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject Cardiology (incl Cardiovascular Diseases)
URI http://hdl.handle.net/10072/28910
Publication Type Letter or Note
Publication Type Code c3

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