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dc.contributor.authorRose'Meyer, Roselynen_US
dc.contributor.authorHeadrick, Johnen_US
dc.description.abstractThe impact of age on functional sensitivity to A1-adenosine receptor activation was studied in Langendorff-perfused hearts from young (1-2 mo) and old (12-18 mo) male Wistar rats. Adenosine mediated bradycardia in young and old hearts, with sensitivity enhanced ~10-fold in old [negative logarithm of EC50(pEC50) = 4.56 ᠰ.11] versus young hearts (pEC50 = 3.70 ᠰ.09). Alternatively, the nonmetabolized A1 agonists N 6-cyclohexyladenosine and (R)-N 6-phenylisopropyladenosine were equipotent in young (pEC50 = 7.43 ᠰ.12 and 6.61 ᠰ.19, respectively) and old hearts (pEC50 = 7.07 ᠰ.10 and 6.80 ᠰ.11, respectively), suggesting a role for uptake and/or catabolism in age-related changes in adenosine sensitivity. In support of this suggestion, [3H]-adenosine uptake was approximately twofold greater in young than in old hearts (from 3-100 占adenosine). However, although inhibition of adenosine deaminase and adenosine transport with 10 卥rythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride and 10 卓-(4-nitrobenzyl)-6-thioinosine increased adenosine sensitivity three- to fourfold, it failed to abolish the sensitivity difference in old (pEC50 = 4.95 ᠰ.08) versus young (pEC50= 4.29 ᠰ.13) hearts. Data indicate that 1) age increases functional A1 receptor sensitivity to adenosine without altering the sensitivity of the A1 receptor itself, and2) age impairs adenosine transport and/or catabolism, but this does not explain differing functional sensitivity to adenosine. This increased functional sensitivity to adenosine may have physiological significance in the older heart.en_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.ispartofjournalAmerican Journal of Physiology: Heart and Circulatory Physiologyen_US
dc.titleAge-related changes in A1 adenosine receptor mediated bradycardiaen_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.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_US
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