MYOCARDIAL ADENOSINE A(1) AND A(2) RECEPTOR ACTIVITIES DURING JUVENILE AND ADULT STAGES OF DEVELOPMENT

Myocardial contractile responsiveness to beta-adrenoceptor stimulation is known to be reduced with maturation or aging. The present study wa s undertaken to determine the role of antiadrenergic A(1) and stimulat ory A(2) adenosine receptors in the modulation of beta-adrenergic-elic ited contractile performance of the heart at juvenile (similar to 25 d ays) and adult (similar to 79 days) stages of maturation. Isoprotereno l, a beta-adrenergic agonist, at 10(-7) M produced a greater maximal i ncrease in contractility, assessed as the maximal rate of left ventric ular pressure development (+ dP/dt(max)), in immature than in mature h earts (104 and 80%, respectively), but produced a greater increase in venous adenosine concentration in the mature than in the immature hear ts (738 and 277 nM, respectively). Isoproterenol at 10(-9) to 10(-8) M produced similar increases in contractility in the absence or presenc e of the A(1) adenosine receptor antagonist xanthine amine congener (X AC; 0.5 mu M) for both immature and mature hearts. In addition, XAC di d not alter the isoproterenol-elicited contractile response in the imm ature 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/dt(max) during hypoperfusion in the presence (79%) vs. the absence (60%) of XAC. In both immature and mature hearts, hypoperfusion enhanced isoproterenol-elicited venous ad enosine concentration by similar magnitudes of 76 and 72%, respectivel y. In further studies, the A(2) 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 matur e but not immature hearts during normal perfusion. These results sugge st that myocardial adenosine modulates the beta-adrenergic-elicited co ntractile response of the adult heart via activation of both A(1) and A(2) adenosine receptors and that these functions of adenosine become expressed with myocardial maturation.