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

M A Bailey, R J Unwin, D G Shirley

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)195-198
Number of pages4
JournalClinical science
Volume101
Issue number2
Publication statusPublished - Aug 2001

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