title: Distal tubular electrolyte transport during inhibition of renal 11beta-hydroxysteroid dehydrogenase.
abstract: To test the proposal that the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) confers aldosterone specificity on mineralocorticoid receptors in the distal nephron by inactivating glucocorticoids, we performed a free-flow micropuncture study of distal tubular function in adrenalectomized rats infused with high-dose corticosterone. One-half of the rats were additionally given intravenous carbenoxolone (CBX; 6 mg/h) to inhibit renal 11beta-HSD activity. Although this maneuver lowered fractional Na(+) excretion (1.1 +/- 0.2 vs. 1.9 +/- 0.2%, P < 0.01), Na(+) reabsorption within the accessible distal tubule was found to be similar in the two groups of animals. In contrast, distal tubular K(+) secretion was enhanced in CBX-treated rats: fractional K(+) deliveries to the early and late distal collection sites in the corticosterone-alone group were 13 +/- 1 and 20 +/- 3%, respectively (not significant), whereas corresponding data in the CBX-treated group were 9 +/- 1 and 24 +/- 2% (P < 0.01). This stimulation of distal K(+) secretion provides the first direct in vivo evidence that 11beta-HSD normally prevents corticosterone from exerting a mineralocorticoid-like effect in the distal tubule. The reduction in fractional Na(+) excretion during inhibition of 11beta-HSD, in the absence of a change in end-distal Na(+) delivery, suggests enhanced Na(+) reabsorption in the collecting ducts.
authors.affiliation: Division of Biomedical Sciences, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RF, United Kingdom.
authors.forename: K J
authors.initials: KJ
authors.lastname: Biller
authors.forename: R J
authors.initials: RJ
authors.lastname: Unwin
authors.forename: D G
authors.initials: DG
authors.lastname: Shirley
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology / Q000502:physiology; D004573:Electrolytes / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006400:Hematocrit; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000378:metabolism
chemical_list: D004573:Electrolytes; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D011188:Potassium; D003345:Corticosterone