Calcium modulation of the renin-aldosterone axis

Changes in the extracellular calcium concentration have important effects on hormone secretion. In vitro, kidney juxtaglomerular cells have been shown to secrete renin in an inverse relationship to the extracellular calcium concentration. The effect of physiologic changes in calcium on renin secretion in humans is less clear. We therefore investigated the effects of physiologic changes in extracellular calcium levels on renin and aldosterone secretion in 7 healthy men. Serum ionized calcium, ACTH, plasma renin activity (PRA), and aldosterone levels were serially measured during 90-min infusions of dextrose, disodium edetate (EDTA) and calcium gluconate, and the latter two infusions were repeated with dexamethasone pre-treatment. ACTH levels decreased during the 5% dextrose in water and the EDTA infusions but increased during the calcium infusion. Similarly, PRA and aldosterone levels fell during the D5W and EDTA infusions but this decrease was absent with increments in calcium levels. Dexamethasone administration suppressed ACTH and the aldosterone response to calcium but did not affect the PRA response to the calcium infusion. Our data indicate that increases in calcium within the physiological range blunt the diurnal decline in both PRA and aldosterone. This appears to be a direct effect of calcium on PRA but mediated through ACTH in the case of aldosterone.