Beta-adrenergic agonist-mediated desensitization in senescent rats

Abstract

The capacity of senescent rats to develop the catecholamine refractory state was investigated in CDF (F-344) rats of 3 and 24 months of age. Beta-adrenergic receptor number, receptor-agonist affinity, and adenylate cyclase activity in heart membranes were assessed, following the chronic in vivo administration of the beta-adrenergic agonist, metaproterenol. Drug treatment leads to marked myocardial hypertrophy, receptor down-regulation, and reduced isoproterenol-stimulated adenylate cyclase activity. The extent of catecholamine-refractoriness was not different in the older rats, indicating the catecholamine desensitization of myocardial beta-adrenergic responsiveness is not impaired in senescence. Receptor agonist affinity and the percent of receptors in the high-affinity state decrease with age. These parameters are further reduced by agonist treatment but to a lesser extent in the older animals. Thus, the effects of age and agonist desensitization are not additive and suggest that aged animals may already be partially desensitized.