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.
|Number of pages||4|
|Publication status||Published - Aug 2001|