Beta-adrenergic agonist-mediated desensitization in senescent rats.
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.
D000262:Adenylyl Cyclases / Q000032:analysis; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D004361:Drug Tolerance; D005260:Female; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009921:Metaproterenol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D009921:Metaproterenol; D000262:Adenylyl Cyclases; D007545:Isoproterenol