Myocardial adenosine A1 and A2 receptor activities during juvenile and adult stages of development

Abstract

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 (approximately 25 days) and adult (approximately 79 days) 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 microM) 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%) vs. 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 microM) 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.