Age-related changes in A1-adenosine receptor-mediated bradycardia

Andrea K. Hinschen, Roselyn B. Rose'Meyer, John P. Headrick
2000 American Journal of Physiology. Heart and Circulatory Physiology  
Age-related changes in A 1 -adenosine receptor-mediated bradycardia. Am. J. Physiol. Heart Circ. Physiol. 278: H789-H795, 2000.-The impact of age on functional sensitivity to A 1 -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 ϳ10-fold in old [negative logarithm of EC 50 (pEC 50 ) ϭ 4.56 Ϯ 0.11] versus young hearts (pEC 50 ϭ 3.70 Ϯ
more » ... s (pEC 50 ϭ 3.70 Ϯ 0.09). Alternatively, the nonmetabolized A 1 agonists N 6 -cyclohexyladenosine and (R)-N 6 -phenylisopropyladenosine were equipotent in young (pEC 50 ϭ 7.43 Ϯ 0.12 and 6.61 Ϯ 0.19, respectively) and old hearts (pEC 50 ϭ 7.07 Ϯ 0.10 and 6.80 Ϯ 0.11, respectively), suggesting a role for uptake and/or catabolism in age-related changes in adenosine sensitivity. In support of this suggestion, [ 3 H]-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 µM erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride and 10 µM S-(4nitrobenzyl)-6-thioinosine increased adenosine sensitivity three-to fourfold, it failed to abolish the sensitivity difference in old (pEC 50 ϭ 4.95 Ϯ 0.08) versus young (pEC 50 ϭ 4.29 Ϯ 0.13) hearts. Data indicate that 1) age increases functional A 1 receptor sensitivity to adenosine without altering the sensitivity of the A 1 receptor itself, and 2) 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.
doi:10.1152/ajpheart.2000.278.3.h789 pmid:10710347 fatcat:supcdpsa4neonfp4l5roikc5zi