VASOPRESSIN POTENTIATES MINERALOCORTICOID SELECTIVITY BY STIMULATING 11-BETA HYDROXYSTEROID DESHYDROGENASE IN RAT COLLECTING DUCT

Arginine vasopressin (AVP) and corticosteroid hormones are involved in sodium reabsorption regulation in the renal collecting duct. Synergy between AVP and aldosterone has been well documented, although its mec hanism remains unclear. Both aldosterone and glucocorticoid hormones b ind to the mineralocorticoid receptor (MR), and mineralocorticoid sele ctivity depends on the MR-protecting enzyme 11 beta hydroxysteroid des hydrogenase (11-HSD), which metabolizes glucocorticoids into derivativ es with low affinity for MR, We have investigated whether the activity of 11-HSD could be influenced by AVP and corticosteroid hormones. Thi s study shows that in isolated rat renal collecting ducts, AVP increas es 11-HSD catalytic activity, This effect is maximal at 10(-8) M AVP ( a concentration clearly above the normal physiological range of AVP co ncentrations) and involves the V2 receptor pathway, while activation o f protein kinase C or changes in intracellular calcium are ineffective , The stimulatory effect of AVP on 11-HSD is largely reduced after adr enalectomy, and is selectively restored by infusion of aldosterone, no t glucocorticoids. We conclude that this synergy between AVP and aldos terone in controlling the activity of 11-HSD is likely to play a pivot al role in resetting mineralocorticoid selectivity, and hence sodium r eabsorption capacities of the renal collecting duct.