Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the guinea pig

Abstract

Redmann A, Möbius K, Hiller HH, Oelkers W, Bähr V. Ascorbate depletion prevents aldosterone stimulation by sodium deficiency in the guinea pig. Eur J Endocrinol 1995;133:499–506. ISSN 0804–4643 The concentration of ascorbic acid (vitamin C) in the adrenal cortex is 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 aldosterone synthesis from damaging lipid peroxides. Alternatively, vitamin C could act as part of an auxiliary electron transport system for the last step of aldosterone synthesis. The effects of vitamin C depletion on adrenocortical function cannot be studied in the human for ethical reasons, so we subjected different groups of guinea pigs to vitamin C depletion, sodium depletion and combined vitamin C and sodium depletion. Other groups of animals on normal or vitamin C-deficient diets received high-dose adrenocorticotrophin (ACTH) injections for 3 days before sacrifice. Fifteen days of a vitamin C-free diet led to very low 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 deficiency. Simultaneous vitamin C depletion completely abolished the rise in aldosterone in vivo and in vitro, significantly reduced the conversion of [3H]deoxycorticosterone to [3H]aldosterone and impaired renal sodium conservation. Plasma renin activity (PRA), plasma ACTH and serum 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 without an increase in ACTH, while in vitro secretion of cortisol was slightly decreased. These findings seem to be due to decreased hepatic cortisol metabolism. Three days of ACTH treatment led to a large increase in plasma cortisol and in vitro cortisol secretion, while plasma aldosterone and in vitro aldosterone secretion (and PRA) were greatly suppressed. This effect of ACTH was not changed by vitamin C depletion. In conclusion, our studies have demonstrated for the first time a permissive role of vitamin C in the adaptation of aldosterone secretion and of sodium excretion to sodium deficiency, which is an important physiological function of aldosterone. The molecular mechanisms by which vitamin C is involved in aldosterone synthesis await further studies. V Bähr, Freie Universität Berlin, Klinikum Benjamin Franklin, Division of Endocrinology, Department of Medicine, Hindenburgdamm 30, D-12200 Berlin, Germany