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

In order to test the proposal that the aldosterone specificity of mineralocorticoid receptors in the collecting duct depends on inactivation of glucocorticoids by the enzyme 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD), we have assessed the effect of pharmacological inhibition of 11 beta -HSD on collecting duct Na+ reabsorption in vivo. Adrenalectomized rats (n = 14) were infused intravenously with high-dose corticosterone, and late-distal tubules were perfused orthogradely with artificial tubular fluid containing [C-14]inulin and Na-22; urinary recoveries of the radioisotopes were monitored. Half of the rats received intravenous carbenoxolone to inhibit renal 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 corticosterone-alone group (54 +/- 4%, P < 0.01). These data, which provide the first demonstration of enhanced Na+ reabsorption in the distal nephron during inhibition of renal 11 beta -HSD in vivo, strongly support the proposal that 11 beta -HSD normally prevents endogenous glucocorticoid from exerting mineralocorticoid-like effects.