Age-related alterations in sympathetic-adrenal medullary responses to stress.

In mammals, aging is often viewed as a progressive decline in physiological competence with a corresponding inability to adapt to stressful stimulation. Several current theories of aging have implicated the sympathetic nervous system in many of the metabolic, cardiovascular and behavior changes which attend advancing age. To provide an empirical base for evaluating the role of the sympathetic nervous system in aging, I have studied the activity of the sympathetic nerves and the adrenal medulla of adult and aged Fischer 344 male rats before, during and after exposure to various stressful stimuli. Plasma levels of norepinephrine and epinephrine served as biochemical indices of the activity of the sympathetic nerves and the adrenal medulla, respectively. Under resting conditions, rats 4-24 months of age had similar plasma levels of both catecholamines. When stressed for a brief period of time (intermittent footshock for 1 min), 12- and 24-month-old rats exhibited a diminished sympathetic-adrenal medullary response compared to young adult rats (4 months old). With an increase in the intensity and duration of the stressor (cold water immersion for 10 min), the sympathetic-adrenal medullary responses of 6- and 22-month-old rats were comparable. However, the sympathetic nervous system remained in a heightened state of activity for a longer period of time following the stressful stimulus in aged rats. Finally, with prolonged exposure to an intense stressor (cellular glucoprivation following administration of 2-deoxy-D-glucose), 24-month-old rats exhibited an exaggerated adrenal medullary response and a greater mortality rate compared to 6-month-old rats. These findings suggest that homeostatic regulation of the sympathetic nervous system is impaired in aged rodents. Further, the nature of this impairment is dependent upon the intensity and duration of the activating stimulus. These apparent age-related alterations in regulation of the sympathetic nervous system may contribute to the increased morbidity and mortality of aged animals during prolonged exposure to stressful stimulation.