Vol. 293, Issue 2, 599-606, May 2000

Effects of Cyclopentyladenosine on Isoproterenol Response in Adult and Senescent Cardiac Tissue from Fischer 344 Rats¹

Chris L. Kapicka , Stephen C. Montamat , Ramagopal V. Mudumbi , Shelley M. Jacks , Richard D. Olson and Robert E. Vestal

Department of Biology, Northwest Nazarene University, Nampa, Idaho (C.L.K.); Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Boise, Idaho (S.C.M., R.V.M., S.M.J., R.D.O., R.E.V.); Mountain States Medical Research Institute, Boise, Idaho (C.L.K., S.C.M., R.V.M., R.D.O., R.E.V.); and Departments of Medicine and Pharmacology, University of Washington School of Medicine, Seattle, Washington (S.M.J., R.D.O., R.E.V.)

To characterize age-related changes in -adrenergic responsiveness and to test the hypothesis that an increase in the effects of adenosine contribute to impaired -adrenergic responsiveness, Fischer 344 rat right atria (RA), left atria (LA), and left ventricular trabeculae carnae were exposed to the -receptor agonist isoproterenol (ISO), followed by four doses of the selective adenosine A₁ receptor agonist cyclopentyladenosine (CPA). Spontaneous contractile rates of adult RA were inhibited more than senescent RA by CPA. Contractility (+dF/dt) of adult LA was reduced more than senescent LA by CPA. Left trabeculae carnae tissue responded weakly to CPA, but senescent tissue was less responsive than adult tissue. Senescent atrial A₁ receptor density was 56% greater than in adult tissue, whereas the density in senescent ventricles was 39% lower than in adult tissue. No significant difference in antagonist affinities (K_d) of A₁ receptor was observed between adult and senescent atria. In addition, agonist competition curves indicated a significant increase in senescent atrial and a decrease in senescent ventricular tissue in the affinity of agonist for high-affinity A₁ receptors with no difference in dissociation constant (K_i). No significant age-related differences in atrial or ventricular tissues occurred in either the antagonist affinity (K_d) or density (B_max) of the -adrenergic receptors. CPA was found to inhibit ISO-stimulated adenylate cyclase activity more in senescent than in adult atrial and ventricular membrane preparations. We conclude that age-related differences in functional response to ISO and CPA, A₁ receptor density, and ISO-stimulated adenylate cyclase activity differ in atrial and ventricular myocardium.