ASCORBATE DEPLETION PREVENTS ALDOSTERONE STIMULATION BY SODIUM DEFICIENCY IN THE GUINEA-PIG

The concentration of ascorbic acid (vitamin C) in the adrenal cortex i s higher than in any other organ. The role of vitamin C in the adrenal cortex is unknown, but data obtained with bovine adrenocortical cells in vitro favour its role as an antioxidant that especially protects a ldosterone synthesis from damaging lipid peroxides. Alternatively, vit amin C could act as part of an auxiliary electron transport system for the last step of aldosterone synthesis. The effects of vitamin C depl etion on adrenocortical function cannot be studied in the human for et hical reasons, so we subjected different groups of guinea pigs to vita min C depletion, sodium depletion and combined vitamin C and sodium de pletion. Other groups of animals on normal or vitamin C-deficient diet s received high-dose adrenocorticotrophin (ACTH) injections for 3 days before sacrifice. Fifteen days of a vitamin C-free diet led to very l ow vitamin C levels in adrenals, liver and plasma without clear signs of scurvy. At this time, plasma aldosterone and aldosterone secretion by isolated adrenal cells were stimulated significantly by sodium defi ciency. Simultaneous vitamin C depletion completely abolished the rise in aldosterone in vivo and in vitro, significantly reduced the conver sion of [H-3]deoxycorticosterone to [H-3]aldosterone and impaired rena l sodium conservation Plasma renin activity (PRA), plasma ACTH and ser um potassium were not different in the sodium-depleted and sodium plus vitamin C-depleted groups. Sodium depletion did not affect cortisol. Vitamin C depletion led to a significant increase in plasma cortisol w ithout an increase in ACTH, while in vitro secretion of cortisol was s lightly decreased. These findings seem to be due to decreased hepatic cortisol metabolism. Three days of ACTH treatment led to a large incre ase in plasma cortisol and in vitro cortisol secretion, while plasma a ldosterone and in vitro aldosterone secretion (and PRA) were greatly s uppressed. This effect of ACTH was not changed by vitamin C depletion. In conclusion, our studies have demonstrated for the first time a per missive role of vitamin C in the adaptation of aldosterone secretion a nd of sodium excretion to sodium deficiency, which is an important phy siological function of aldosterone. The molecular mechanisms by which vitamin C is involved in aldosterone synthesis await further studies.