Effects of cyclopentyladenosine on isoproterenol response in adult and senescent cardiac tissue from Fischer 344 rats

To characterize age-related changes in beta-adrenergic responsiveness and t o test the hypothesis that an increase in the effects of adenosine contribu te to impaired beta-adrenergic responsiveness, Fischer 344 rat right atria (RA), left atria (LA), and left ventricular trabeculae carnae were exposed to the beta-receptor agonist isoproterenol (ISO), followed by four doses of the selective adenosine A(1) receptor agonist cyclopentyladenosine (CPA). Spontaneous contractile rates of adult RA were inhibited more than senescen t RA by CPA. Contractility (+dF/dt) of adult LA was reduced more than senes cent LA by CPA. Left trabeculae carnae tissue responded weakly to CPA, but senescent tissue was less responsive than adult tissue. Senescent atrial A( 1) receptor density was 56% greater than in adult tissue, whereas the densi ty in senescent ventricles was 39% lower than in adult tissue. No significa nt difference in antagonist affinities (K-d) of A(1) receptor was observed between adult and senescent atria. In addition, agonist competition curves indicated a significant increase in senescent atrial and a decrease in sene scent ventricular tissue in the affinity of agonist for high-affinity A(1) receptors with no difference in dissociation constant (K-i). No significant age-related differences in atrial or ventricular tissues occurred in eithe r the antagonist affinity (K-d) or density (B-max) of the beta-adrenergic r eceptors. CPA was found to inhibit ISO-stimulated adenylate cyclase activit y more in senescent than in adult atrial and ventricular membrane preparati ons. We conclude that age-related differences in functional response to ISO and CPA, A(1) receptor density, and ISO-stimulated adenylate cyclase activ ity differ in atrial and ventricular myocardium.