EFFECTS OF AGING ON EPINEPHRINE SECRETION AND REGIONAL RELEASE OF EPINEPHRINE FROM THE HUMAN HEART

In contrast to the sympathetic nervous system, which is activated by a ging in at least some sympathetic nervous outflows, epinephrine releas e from the adrenal medulla appears to be either normal or low in the e lderly. Using isotope dilution methodology, we studied the effect of a ging on the secretion of epinephrine in 19 men, aged 20-30 yr, and 15 men, aged 60-75 yr. Measurements were made both at rest and during the application of laboratory stressors, as diminished adrenal medullary responsiveness possibly contributes to the impairment of some cardiova scular and metabolic responses to stress described previously in the e lderly. Epinephrine secretion at rest was lower in the older men (mean +/- SEM, 0.86 +/- 0.10 nmol/min) than in the younger men (1.45 +/- 0. 17 nmol/min; P < 0.05). Due to 20% lower plasma epinephrine clearance in the older men (P < 0.01), the reduction in the plasma concentration of epinephrine (0.37 +/- 0.03 vs. 0.52 +/- 0.06 nmol/L; P = 0.06) was proportionally less than that in epinephrine secretion. In the younge r men, epinephrine secretion doubled or tripled during mental stress, isometric exercise, and dynamic exercise. Epinephrine responses to the stressors were reduced in older men, being equivalent to only 44% (P < 0.05), 44% (P = 0.1), and 33% (P = 0.01) of the corresponding respon ses in the younger men. After uptake from plasma, in some circumstance s epinephrine is released from sympathetic nerves as a cotransmitter, where it can augment the release of the major sympathetic transmitter, norepinephrine. We also measured regional extraadrenal release of epi nephrine from the heart to test whether the previously described incre ased release of norepinephrine from the cardiac sympathetic nerves wit h aging might result from facilitator effects of epinephrine released as a cotransmitter. At rest, epinephrine was released from the heart ( 9.4 +/- 2.6 pmol/min) in older men only (P < 0.01) despite the fact th at adrenal medullary secretion of epinephrine was reduced. Failure of epinephrine and norepinephrine spillover from the heart to increase in parallel in the elderly during the sympathetic excitation accompanyin g exercise suggested that epinephrine lay outside the sympathetic nerv es, perhaps arising from extraneuronal synthesis in the heart. We have not yet tested whether extraneuronal, in contrast to neuronal, epinep hrine release in the heart could contribute to the observed higher rat es of norepinephrine release in the elderly.