Age-related reduction of beta-adrenoceptor sensitivity in rat heart occurs by multiple mechanisms

Myocardial responsiveness to catecholamines was evaluated by measuring isoproterenol-stimulated adenylate cyclase activities in myocardial particulate fractions from Fischer 344 rats of 3, 12, and 24 months of age. Dose-response curves of isoproterenol revealed a progressive increase in the activation constant (Kact) with advancing age. In addition, the maximal velocity (Vmax) for 12- and 24-month-old groups was about 20-25% lower than for the 3-month-old group. Analysis of receptor-binding data and nonreceptor-mediated enzyme activities suggests that the age-related decrease in Vmax for isoproterenol may result from a loss of myocardial beta-receptors, whereas the increase in Kact is probably due to a deficit in the postreceptor components of the receptor-cyclase complex.