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dc.contributor.authorZatta, Amandaen_US
dc.contributor.authorWillems, Lauraen_US
dc.contributor.authorHeadrick, Johnen_US
dc.description.abstractObjectives: 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 20-25-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 8.4ᰮ1 and 7.4ᰮ1 in non-ischemic hearts versus 7.7ᰮ1 and 7.1ᰮ1 after 20-min ischemia (P<0.05). Sensitivity was further reduced after 25-min ischemia. Responses to nitroprusside were unaltered. NO-synthase antagonism (50 占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 占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.en_US
dc.publisherElsevier Scienceen_US
dc.relation.ispartofjournalCardiovascular Researchen_US
dc.titleCoronary function and adenosine receptor-mediated responses in ischemic reperfused mouse hearten_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightCopyright 2002 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.en_AU
gro.hasfulltextNo Full Text

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