AJP - Heart and Circulatory Physiology, Vol 270, Issue 3 897-H906, Copyright © 1996 by American Physiological Society

ARTICLES

Impact of aging on adenosine levels, A1/A2 responses, arrhythmogenesis, and energy metabolism in rat heart

J. P. Headrick
Department of Molecular Sciences, James Cook University of North Queensland, Townsville, Australia.

Adenosine formation, energy metabolism, A1 and A2 responses, and arrhythmogenesis were examined in hearts from young adult (4-6 mo) and aged rats (18-20 mo). Aging reduced heart rate from 308 +/- 9 to 252 +/- 13 beats/min and myocardial O2 consumption (MVO2) from 127 +/- 5 to 103 +/- 4 microliters O2.min-1.g-1 and increased atrioventricular conduction time from 47 +/- 4 to 61 +/- 8 ms. Differences in intrinsic rate were reduced by A1 antagonism with 10 microM 8-cyclopentyl-1,3-dimethylxanthine. Adenosine efflux and cardiac microdialysate [adenosine] in isovolumically working hearts increased twofold with aging, despite reduced MVO2. Enhanced [adenosine] was not due to altered uptake and catabolism but was associated with twofold higher cytosolic adenosine 5'-monophosphate concentration despite comparable energy state (free energy of ATP hydrolysis = -62.25 +/- 0.38 and -61.78 +/- 0.46 kJ/mol in young adult and aged hearts, respectively). Bradycardia (presumably A1 mediated) was 10-fold more sensitive in aged [-log dose required to produce 50% ectopy (pEC50) = 4.9 +/- 0.1] than in young adult hearts (pEC50 = 3.9 +/- 0.1). Adenosine also became potently arrhythmogenic with aging (-log dose required to produce 20% ectopy = 3.6 +/- 0.3 in young adult and 5.3 +/- 0.2 and aged hearts). Alternatively, vasodilation (presumably A2 mediated) was less sensitive with aging (pEC50 = 6.1 +/- 0.1 in young adult and 4.5 +/- 0.1 in aged hearts; pEC50 = 3.8 +/- 0.1 in young adult and 3.1 +/- 0.1 in aged aortic rings). The data indicate that aging 1) enhances interstitial [adenosine], probably via elevated myocardial adenosine 5'-monophosphate concentration, 2) enhances A1 sensitivity and arrhythmogenesis, and 3) reduces adenosine A2 sensitivity. These changes contribute to altered cardiovascular function in aged hearts.

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