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dc.contributor.authorWillems, Lauraen_US
dc.contributor.authorReichelt, Melissaen_US
dc.contributor.authorMolina, Joseen_US
dc.contributor.authorSun, Chun-Xiaoen_US
dc.contributor.authorChunn, Jancien_US
dc.contributor.authorAshton, Kevinen_US
dc.contributor.authorSchnermann, Jurgenen_US
dc.contributor.authorBlackburn, Michaelen_US
dc.contributor.authorHeadrick, Johnen_US
dc.contributor.editorHans Michael Piperen_US
dc.date.accessioned2017-04-24T08:09:09Z
dc.date.available2017-04-24T08:09:09Z
dc.date.issued2006en_US
dc.date.modified2007-08-07T04:47:31Z
dc.identifier.issn00086363en_US
dc.identifier.urihttp://hdl.handle.net/10072/14271
dc.description.abstractOBJECTIVE: Adenosine deaminase (ADA) may be multifunctional, regulating adenosine levels and adenosine receptor (AR) agonism, and potentially modifying AR functionality. Herein we assess effects of ADA (and A(1)AR) deficiency on AR-mediated responses and ischaemic tolerance. METHODS: Normoxic function and responses to 20 or 25min ischaemia and 45min reperfusion were studied in isolated hearts from wild-type mice and from mice deficient in ADA and/or A(1)ARs. RESULTS: Neither ADA or A(1)AR deficiency significantly modified basal contractility, although ADA deficiency reduced resting heart rate (an effect abrogated by A(1)AR deficiency). Bradycardia and vasodilation in response to AR agonism (2-chloroadenosine) were unaltered by ADA deficiency, while A(1)AR deficiency eliminated the heart rate response. Adenosine efflux increased 10- to 20-fold with ADA deficiency (at the expense of inosine). Deletion of ADA improved outcome from 25min ischaemia, reducing ventricular diastolic pressure (by 45%; 21+/-4 vs. 38+/-3mm Hg) and lactate dehydrogenase (LDH) efflux (by 40%; 0.12+/-0.01 vs. 0.21+/-0.02U/g/min ischaemia), and enhancing pressure development (by 35%; 89+/-6 vs. 66+/-5mm Hg). Similar protection was evident after 20min ischaemia, and was mimicked by the ADA inhibitor EHNA (5muM). Deletion of ADA also enhanced tolerance in A(1)AR deficient hearts, though effects on diastolic pressure were eliminated. CONCLUSIONS: Deficiency of ADA does not alter sensitivities of cardiovascular A(1) or A(2)ARs (despite markedly elevated [adenosine]), but significantly improves ischaemic tolerance. Conversely, A(1)AR deficiency impairs ischaemic tolerance. Effects of ADA deficiency on diastolic pressure appear solely A(1)AR-dependent while other ARs or processes additionally contribute to improved contractile recovery and reduced cell death.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherElsevier BVen_US
dc.publisher.placeNetherlandsen_US
dc.relation.ispartofstudentpublicationYen_AU
dc.relation.ispartofpagefrom79en_US
dc.relation.ispartofpageto87en_US
dc.relation.ispartofedition2006en_US
dc.relation.ispartofissue1en_US
dc.relation.ispartofjournalCardiovascular Researchen_US
dc.relation.ispartofvolume71en_US
dc.rights.retentionNen_AU
dc.subject.fieldofresearchcode270102en_US
dc.subject.fieldofresearchcode320603en_US
dc.titleEffects of adenosine deaminase and A1 receptor deficiency in normoxic and ischaemic mouse heartsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2006
gro.hasfulltextNo Full Text


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