Myocardial adenosine a1 and a2 receptor activities increase between juvenile and adult stages of development. Sawmiller, Darrell R., Richard A. Fenton, and James G. Dobson, Jr. Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts
APStracts 2:0535H, 1995.
Myocardial contractile responsiveness to [beta]-adrenoceptor stimulation is known to be reduced with maturation or aging. The present study was undertaken to determine the role of antiadrenergic A1 and stimulatory A2 adenosine receptors in the modulation of [beta]-adrenergic-elicited contractile performance of the heart at juvenile (ca. 25 d) and adult (ca. 79 d) stages of maturation. Isoproterenol, a [beta]-adrenergic agonist, at 10-7 M produced a greater maximal increase in contractility, assessed as the maximal rate of left ventricular pressure development (+dP/dtmax), in immature than in mature hearts (104% and 80% respectively), but produced a greater increase in venous adenosine concentration in the mature than in the immature hearts (738 and 277 nM respectively). Isoproterenol at 10-9 to 10-8 M produced similar increases in contractility in the absence or presence of the A1 adenosine receptor antagonist xanthine amine congener (XAC, 0.5 [mu]M) for both immature and mature hearts. In addition, XAC did not alter the isoproterenol -elicited contractile response in the immature heart during hypoperfusion induced by 50% reduction of coronary flow. However, in the mature heart, 10-8 M isoproterenol elicited a significantly greater increase in +dP/dtmax during hypoperfusion in the presence (79%) versus the absence (60%) of XAC. In both immature and mature hearts, hypoperfusion enhanced isoproterenol-elicited venous adenosine concentration by similar magnitudes of 76% and 72%, respectively. In further studies, the A2 adenosine receptor antagonist, 9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5 -amine (CGS-15943, 1 [mu]M), reduced the isoproterenol-elicited contractile response of mature but not immature hearts during normal perfusion. These results suggest that myocardial adenosine modulates the [beta]-adrenergic-elicited contractile response of the adult heart via activation of both A1 and A2 adenosine receptors and that these functions of adenosine become expressed with myocardial maturation. 

Received 22 June 1995; accepted in final form 17 November 1995.
APS Manuscript Number H569-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95