Effects of A3 adenosine receptor activation and gene knock-out in ischemic-reperfused mouse heart

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Title Effects of A3 adenosine receptor activation and gene knock-out in ischemic-reperfused mouse heart
Author Harrison, Glenn; Cerniway, Rachael J; Peart, Jason Nigel John; Berr, Stuart S; Ashton, Kevin John; Regan, Sara; Matherne, G Paul; Headrick, John Patrick
Journal Name Cardiovascular Research
Year Published 2002
Place of publication Netherlands
Publisher Elsevier Science
Abstract Objectives: To characterize effects of A3 adenosine receptor (A3AR) activation and gene knock-out on responses to ischemia-reperfusion in mouse heart. Methods: Perfused hearts from wild-type and A3AR gene knock-out (A3AR KO) mice were subjected to 20 min ischemia and 30 min reperfusion. Functional responses were assessed and changes in energy metabolism and cytosolic pH monitored via 31P-NMR spectroscopy. Results: Selective A3AR agonism with 100 nM 2-chloro-N6-(3-iodobenzyl)-adenosine-52-N-methyluronamide (chloro-IB-MECA) enhanced post-ischemic contractile recovery without altering contracture development in wild-type hearts, an effect unrelated to non-selective activation of A1 or A2 adenosine receptors. Chloro-IB-MECA also improved recovery in hearts overexpressing A1ARs. Paradoxically, post-ischemic recovery was enhanced by A3AR KO. Developed pressure, +dP/dt, and dP/dt all recovered to higher levels in A3AR KO (7080% of pre-ischemia) vs. wild-type hearts (4550% of pre-ischemia) (P<0.05). Enhanced recovery was unrelated to recoveries of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), energy state ([ATP]/[ADP]. [Pi], ”GATP) or cytosolic pH. Conclusions: Selective A3AR activation is cardioprotective in wild-type hearts and hearts overexpressing A1ARs, yet A3AR gene deletion generates an ischemia-tolerant phenotype without altering energy metabolism or pH. This may be due to compensatory changes or undefined genotypic differences in A3AR KO vs. wild-type hearts.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.elsevier.com/wps/find/journaldescription.cws_home/525398/description#description
Copyright Statement Copyright 2003 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
Volume 53
Page from 147
Page to 155
ISSN 0008-6363
Date Accessioned 2003-03-20
Language en_AU
Research Centre Heart Foundation Research Centre; Griffith Health Institute
Faculty Griffith Health Faculty
Subject Cardiology (incl. Cardiovascular Diseases)
URI http://hdl.handle.net/10072/6839
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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