Effects of aging on adenosine levels, a1 and a2 responses,
arrhythmogenesis and energy metabolism in rat heart.
Headrick, John P.
Division of Biochemistry & Human Physiology, Department of
Molecular Sciences, James Cook University of North Queensland,
Townsville, Queensland 4811, Australia
APStracts 2:0399H, 1995.
Adenosine formation, energy metabolism, A1 and A2 responses, and
arrhythmogenesis were examined in hearts from young adult (4-6
months) and aged rats (18-20 months). Aging reduced heart rate from
308+/-9 to 252+/-13 beats.min-1 and MVO2 from 127+/-5 to 103+/-4
[mu]l 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 [mu]M 8-cyclopentyl-1,3- dimethylxanthine.
Adenosine efflux and cardiac microdialysate [adenosine] in
isovolumically working hearts increased 2-fold with aging, despite
reduced MVO2. Enhanced [adenosine] was not due to altered uptake and
catabolism, but was associated with 2-fold higher cytosolic [5'-AMP]
despite comparable energy state (_GATP = -62.25+/-0.38 in young
adult, -61.78+/-0.46 kJ.mol-1 in aged hearts). Bradycardia
(presumably A1-mediated) was 10-fold more sensitive in aged (pEC50 =
4.9+/-0.1) compared with young adult hearts (pEC50 = 3.9+/-0.1).
Adenosine also became potently arrhythmogenic with aging (pEC20 for
ectopy = 3.6+/-0.3 in young adult, 5.3+/-0.2 in aged hearts).
Alternatively, vasodilatation (presumably A2-mediated) was less
sensitive with aging (pEC50 = 6.1+/-0.1 in young adult, 4.5+/-0.1 in
aged hearts; pEC50 = 3.8+/-0.1 in young adult, 3.1+/-0.1 in aged
aortic rings). The data indicate that aging: i) enhances interstitial
[adenosine], probably via elevated myocardial [5'-AMP], ii) enhances
A1 sensitivity and arrhythmogenesis, and iii) reduces adenosine A2
sensitivity. These changes contribute to altered cardiovascular
function in aged hearts.
Received 15 May 1995; accepted in final form 29 August 1995.
APS Manuscript Number H458-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.