Effect of age on adrenergic neuronal uptake in rat heart

Cardiovascular responsiveness to sympathetic influences is reduced with increasing age. This reduced responsiveness may reflect alterations in effector mechanisms or in neurohumoral transmission processes. We investigated the effect of age on the cardiac adrenergic neuronal uptake mechanism in the Fischer 344 rat by measuring the cocaine-induced potentiation of norepinephrine (NE) positive chronotropic responses. Hearts from male rats (6, 12 and 24 months old) were perfused according to a modified method of Langendorff. For each heart, chronotropic responses to increasing doses of NE were obtained. After this, hearts were perfused with 1 microM cocaine to block the neuronal uptake of NE. A second series of NE doses were administered and heart rate (HR) responses measured. Under control perfusion conditions, HR responses to NE decreased with increasing age. In the presence of cocaine, HR responses to NE were significantly augmented in the 12 and 24 months rat hearts, but not in the 6 months rat hearts. However, the cocaine-potentiated responses to NE at 12 and 24 months did not exceed responses to NE alone at 6 months. In a separate series of experiments, HR responses to isoproterenol were not modified by cocaine at any age. These results indicate that activity of neuronal uptake pump is greater in the 12 and 24 months rats than in the 6 months rats. This increased uptake activity may account at least in part for the reduced responsiveness of older hearts to NE.