In vivo inhibition of renal 11,beta-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption

In order to test the proposal that the aldosterone specificity of mineraloc orticoid receptors in the collecting duct depends on inactivation of glucoc orticoids by the enzyme 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD ), we have assessed the effect of pharmacological inhibition of 11 beta -HS D on collecting duct Na+ reabsorption in vivo. Adrenalectomized rats (n = 1 4) were infused intravenously with high-dose corticosterone, and late-dista l tubules were perfused orthogradely with artificial tubular fluid containi ng [C-14]inulin and Na-22; urinary recoveries of the radioisotopes were mon itored. Half of the rats received intravenous carbenoxolone to inhibit rena l 11 beta -HSD activity. The urinary recovery of [C-14]inulin was complete in both groups of animals (101 +/- 2% versus 101 +/- 3%), but the recovery of Na-22 was lower in carbenoxolone-treated rats (34 +/- 5%) than in the co rticosterone-alone group (54 +/- 4%, P < 0.01). These data, which provide t he first demonstration of enhanced Na+ reabsorption in the distal nephron d uring inhibition of renal 11 beta -HSD in vivo, strongly support the propos al that 11 beta -HSD normally prevents endogenous glucocorticoid from exert ing mineralocorticoid-like effects.