ASCORBATE AND ALPHA-TOCOPHEROL DEPLETION INHIBIT ALDOSTERONE STIMULATION BY SODIUM DEFICIENCY IN THE GUINEA-PIG

Ascorbate (Vit.C) and alpha - tocopherol (Vit.E) are highly concentrat ed in the adrenal. Both vitamins support steroid synthesis in vitro. V itamin depletion experiments in guinea pigs were done to study the rol e in aldosterone synthesis of these antioxidants in vivo. We stimulate d aldosterone secretion by sodium depletion in vitamin depleted animal s and compared the effects with those in vitamin replete guinea pigs. We analysed plasma hormone levels and measured ex vivo steroid secreti on by isolated adrenal cells and conversion of [H-3]deoxycorticosteron e to [H-3]aldosterone. Fifteen days of a Vit.C - free diet led to very low Vit.C levels in adrenals, liver and plasma, without signs of scur vy. Plasma ACTH and plasma renin activity (PRA) were not influenced. V it.C depletion abolished a rise of plasma aldosterone and of aldostero ne secreted in vitro stimulated by sodium depletion. The in vitro conv ersion of [H-3]deoxycorticosterone to [H-3]aldosterone was reduced and sodium conservation was impaired by Vit.C depletion. Vit.E depletion did not abolish but significantly attenuated the rise in plasma aldost erone stimulated by sodium depletion. Aldosterone secretion by adrenal cells isolated from these animals was suppressed to control levels. B oth antioxidants Vit.C and Vit.E seem to play a permissive role in ald osterone synthesis, possibly by protecting the cytochrome P450(11 beta ) from lipidperoxides. Vit.C may also act as part of an auxiliary elec tron transport system for the last step of aldosterone synthesis.