Coronary function and adenosine receptor-mediated responses in ischemic reperfused mouse heart

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Title Coronary function and adenosine receptor-mediated responses in ischemic reperfused mouse heart
Author Zatta, Amanda Jane; Willems, Laura; Headrick, John Patrick
Journal Name Cardiovascular Research
Year Published 2002
Place of publication Netherlands
Publisher Elsevier Science
Abstract Objectives: To assess the impact of ischemia-reperfusion (I/R) on coronary function, and the role of endogenous adenosine in modifying post-ischemic vascular function in asanguinous hearts. Methods: Vascular function was studied in Langendorff perfused mouse hearts subjected to 2025-min ischemia and 30-min reperfusion. Results: Ischemia altered the dependence of flow on work-rate observed in normoxic hearts, and inhibited reflow by mechanisms additional to diastolic compression. Coronary responses were selectively reduced: 2-chloroadenosine and ADP dilated with pEC50s of 8.4±0.1 and 7.4±0.1 in non-ischemic hearts versus 7.7±0.1 and 7.1±0.1 after 20-min ischemia (P<0.05). Sensitivity was further reduced after 25-min ischemia. Responses to nitroprusside were unaltered. NO-synthase antagonism (50 ¼M nitro--arginine methylester) reduced sensitivities to 2-chloroadenosine and ADP up to 10-fold, and eliminated inhibitory effects of I/R. KATP blockade with 5 ¼M glibenclamide impaired sensitivity pre- and post-ischemia, not eliminating the inhibitory effects of I/R. A1 adenosine receptor antagonism with 100 nM 8-cyclopentyl-1,3-dipropylxanthine worsened effects of ischemia on sensitivity. A2A adenosine receptor antagonism with 100 nM 8-(3-chlorostyryl)caffeine reduced post-ischemic flow by 50%, yet paradoxically enhanced post-ischemic contractile recovery. Conclusions: Ischemia modifies vascular control and impairs NO- versus KATP-dependent coronary dilation in an asanguinous model. Endogenous adenosine protects against vascular dysfunction via A1 receptors, and determines coronary reflow via A2A receptors. However, intrinsic A2A activation apparently worsens contractile dysfunction.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.elsevier.com/wps/find/journaldescription.cws_home/525398/description#description
Copyright Statement Copyright 2002 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
Volume 55
Page from 161
Page to 170
ISSN 0008-6363
Date Accessioned 2003-04-16
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/10072/6797
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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