title: In vivo inhibition of renal 11beta-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption.
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 11beta-hydroxysteroid dehydrogenase (11beta-HSD), we have assessed the effect of pharmacological inhibition of 11beta-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 [14C]inulin and 22Na; urinary recoveries of the radioisotopes were monitored. Half of the rats received intravenous carbenoxolone to inhibit renal 11beta-HSD activity. The urinary recovery of [14C]inulin was complete in both groups of animals (101+/-2% versus 101+/-3%), but the recovery of 22Na 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 11beta-HSD in vivo, strongly support the proposal that 11beta-HSD normally prevents endogenous glucocorticoid from exerting mineralocorticoid-like effects.
authors.affiliation: Centre for Nephrology, Institute of Urology and Nephrology, Middlesex Hospital, Mortimer Street, London W1N 8AA, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Bailey
authors.forename: R J
authors.initials: RJ
authors.lastname: Unwin
authors.forename: D G
authors.initials: DG
authors.lastname: Shirley
mesh_terms: D000042:Absorption; D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002229:Carbenoxolone / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D003345:Corticosterone / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D010783:Photometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000493:pharmacokinetics*; D012979:Sodium Radioisotopes / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D012979:Sodium Radioisotopes; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D003345:Corticosterone