MYOCARDIAL ADENOSINE A(1)-RECEPTOR SENSITIVITY DURING JUVENILE AND ADULT STAGES OF MATURATION

In the heart, endogenous adenosine attenuates the beta-adrenergic-elic ited increase in contractile performance via activation of adenosine A (1) receptors. It has been recently reported that this function of ade nosine becomes more pronounced with myocardial maturation. The purpose of the present study was to determine whether mature hearts possess a greater sensitivity than immature hearts to this antiadrenergic effec t of adenosine. Isolated perfused hearts or atria from immature (ca. 2 3 days) and mature (ca. 80 days) rats were stimulated with isoproteren ol(Iso), a beta-adrenergic agonist, at 10(-8) M and concomitantly expo sed to increasing concentrations of 2-chloro-N-6-cyclopentyladenosine (CCPA), a highly selective and potent adenosine A(1)-receptor agonist, from 10(-12) to 10(-6) M. CCPA at 10(-10)-10(-6) M dose dependently r educed the Iso-elicited contractile response more in immature than in mature hearts or atria. At 10(-6) M, CCPA reduced the Iso-elicited con tractile response by 103% in immature hearts and by 55% in mature hear ts. These effects of CCPA were attenuated by the adenosine A(1)-recept or antagonist 8-cyclopentyl-1,3-dipropylxanthine at 10(-7) M. In addit ional experiments, CCPA exhibited similar effectiveness in reducing th e spontaneous heart rate of immature and mature hearts, an effect also mediated by activation of adenosine A(1) receptors. Similar to CCPA, the adenosine A(1)-receptor agonist R-N-6-(2-phenylisopropyl)adenosine reduced the Iso-elicited contractile response more in immature than i n mature hearts, albeit with less effectiveness than CCPA. In agreemen t with these results, CCPA reduced Iso-elicited adenylyl cyclase activ ity more in immature than in mature hearts. Overall, in contrast with our original hypothesis, these results indicate that immature hearts d isplay greater sensitivity than mature hearts to the antiadrenergic ef fect of adenosine A(1)-receptor activation.