Age-associated decrease of adenylate cyclase activity in rat myocardium

Myocardial inotropic and chronotropic responses to beta-adrenergic agonists are diminished with aging. Since myocardial beta-adrenergic receptors are unaltered with age, we tested the hypothesis that this decreased responsiveness is related to a defect in the adenylate cyclase system. Isoproterenol-stimulated adenylate cyclase activity was assessed in myocardial membranes from Fischer 344 rats of 3, 12, and 24 months of age. Basal, as well as F-, GTP-, and hormone-stimulated adenylate cyclase activity was decreased by 20-30% with age. The Km of the enzyme for ATP was not found to be statistically different for any age group studied. These data support the hypothesis that the diminished responsiveness seen in senescence is a result of an alteration in either the catalytic subunit or the coupling protein (N) of the adenylate cyclase complex.