Isoproterenol Responsiveness and Myocardial -Adrenergic Receptors in Young and Old Rats

Abstract

To elucidate the association of β-adrenergic receptors with decreased myocardial catecholamine responsiveness in aging, we investigated the chronotropic response to isoproterenol and myocardial β-adrenergic receptors in fisher 344 rats of 3, 12, and 24 months of age. Heart rate response to isoproterenol (50 μug/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 heart rates (p < .025) and increment over pretreatment, basal minus isoproterenol-stimulated heart rates (p < .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 < .05, .005, respectively) and increments (p < .005, .001, respectively). There were no changes in the density or affinity of myocardial, lymphocytic, or pulmonary β-adrenergic receptors as measured by [³H]-dihydroalprenolol binding in the three age groups investigated. Our data are consistent with the concept that the β-adrenergic stimulatory pathway is unpaired with age. The demonstration of unaltered myocardial β-adrenergic receptor number and affinity with age suggests that myocardial catecholamine responsiveness is impaired at a level other than the β-adrenergic receptor site.