Distal tubular electrolyte transport during inhibition of renal 11 beta-hydroxysteroid dehydrogenase

To test the proposal that the enzyme 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) confers aldosterone specificity on mineralocorticoid recepto rs in the distal nephron by inactivating glucocorticoids, we performed a fr ee-flow micropuncture study of distal tubular function in adrenalectomized rats infused with high-dose corticosterone. One-half of the rats were addit ionally given intravenous carbenoxolone (CBX; 6 mg/h) to inhibit renal 11 b eta -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 acces sible distal tubule was found to be similar in the two groups of animals. I n contrast, distal tubular K+ secretion was enhanced in CBX-treated rats: f ractional K+ deliveries to the early and late distal collection sites in th e 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 prov ides the first direct in vivo evidence that 11 beta -HSD normally prevents corticosterone from exerting a mineralocorticoid-like effect in the distal tubule. The reduction in fractional Na+ excretion during inhibition of 11 b eta -HSD, in the absence of a change in end-distal Na+ delivery, suggests e nhanced Na+ reabsorption in the collecting ducts.