Influence of sodium homeostasis and circadian rhythm on dopaminergic modulation of 18-hydroxycorticosterone secretion in man.

Abstract

This study examines the effects of sodium homeostasis and circadian rhythm on plasma 18-hydroxycorticosterone (18-OHB) responses to the dopamine antagonist metoclopramide in seven normal individuals. Responses to metoclopramide were evaluated after receiving a 10-meq sodium diet, a 100-meq sodium diet, and a 200-meq sodium diet for 5 days. On all three occasions the subjects had reached sodium equilibrium states, as determined by urinary sodium measurements, at the time that they received metoclopramide. Percentage incremental 18-OHB responses to metoclopramide were greater (P less than 0.01) in the subjects after 5 days on a 200-meq sodium intake than after 5 days on a 10-meq sodium intake. The percentage increases in plasma 18-OHB after a 200-meq sodium intake were slightly greater (P less than 0.05) than increases after a 100-meq sodium intake. Plasma 18-OHB levels demonstrated a circadian rhythm, with plasma levels reaching their zenith during the later part of sleep and shortly after awakening and reaching their nadir between 2000 and 2400 h. Although basal levels of 18-OHB at 2200 h (15.5 +/- 1.6 ng/dl) were considerably lower (P less than 0.01) than basal levels of 18-OHB at 0800 h, the 18-OHB responses to metoclopramide were similar at 0800 and 2200 h. Administration of the dopamine agonist bromocriptine (2.5 mg three times a day for 4 days) suppressed (P less than 0.01) mean 24-h plasma 18-OHB levels from 21.9 +/- 2.0 to 14.8 +/- 1.4 ng/dl. However, bromocriptine did not alter the circadian rhythm of 18-OHB secretion. These data suggest that increased sodium intake leads to greater tonic dopaminergic inhibition of 18-OHB secretion. Although dopaminergic mechanisms modulate 18-OHB secretion, they do not govern the circadian rhythm of this corticosteroid.