Isoproterenol responsiveness and myocardial beta-adrenergic receptors in young and old rats

To elucidate the association of beta-adrenergic receptors with decreased myocardial catecholamine responsiveness in aging, we investigated the chronotropic response to isoproterenol and myocardial beta-adrenergic receptors in Fisher 344 rats of 3, 12, and 24 months of age. Heart rate response to isoproterenol (50 mug/kg, subcutaneously) was greatest in 3-month-old animals, both in maximum heart rate achieved and increment over baseline. Twelve-month-old animals had significantly lower maximal hear rates (p less than .025) and increment over pretreatment, basal minus isoproterenol-stimulated heart rates (p less than .005), when compared with 3-month-old animals. Twenty-four-month-old rats were less responsive than either 12- or 3-month-old animals both with respect to maximal rates (p less than .05, .005, respectively) and increments (p less than .005, .001, respectively). There were no changes in the density or affinity of myocardial, lymphocytic, or pulmonary beta-adrenergic receptors as measured by [3H]-dihydroalprenolol binding in the three age groups investigated. Our data are consistent with the concept that the beta-adrenergic stimulatory pathway is impaired with age. The demonstration of unaltered myocardial beta-adrenergic receptor number and affinity with age suggests that myocardial catecholamine responsiveness is impaired at a level other than the beta-adrenergic receptor site.