Age-related changes in A1 adenosine receptor mediated bradycardia

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Title Age-related changes in A1 adenosine receptor mediated bradycardia
Author Hinschen, Andrea; Rose'Meyer, Roselyn; Headrick, John Patrick
Journal Name American Journal of Physiology: Heart and Circulatory Physiology
Year Published 2000
Place of publication USA
Publisher American Physiological Society
Abstract The 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 ± 0.11] versus young hearts (pEC50 = 3.70 ± 0.09). Alternatively, the nonmetabolized A1 agonists N 6-cyclohexyladenosine and (R)-N 6-phenylisopropyladenosine were equipotent in young (pEC50 = 7.43 ± 0.12 and 6.61 ± 0.19, respectively) and old hearts (pEC50 = 7.07 ± 0.10 and 6.80 ± 0.11, 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 μM adenosine). However, although inhibition of adenosine deaminase and adenosine transport with 10 μMerythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride and 10 μMS-(4-nitrobenzyl)-6-thioinosine increased adenosine sensitivity three- to fourfold, it failed to abolish the sensitivity difference in old (pEC50 = 4.95 ± 0.08) versus young (pEC50= 4.29 ± 0.13) 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.
Peer Reviewed Yes
Published Yes
Publisher URI http://ajpheart.physiology.org/content/278/3/H789
Copyright Statement Self-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.
Volume 278
Page from H789
Page to H795
ISSN 0363-6135
Date Accessioned 2001-01-01
Date Available 2015-02-05T03:42:11Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Subject PRE2009-Medical & Health Sciences
URI http://hdl.handle.net/10072/3452
Publication Type Article in Scholarly Refereed Journal
Publication Type Code c1

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