Effects of changes in dietary intake of sodium and potassium and of metabolic acidosis on 11beta-hydroxysteroid dehydrogenase activities in rat kidney.
OBJECTIVE
Glucocorticoid activity is modulated by NADP(+)- and NAD(+)-dependent isoforms of the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD) which convert glucocorticoids to their inactive metabolites. The NAD(+)-dependent isoform, 11betaHSD2, is present in the distal nephron where it confers aldosterone specificity on mineralocorticoid receptors. The objective of this study was to establish whether renal 11betaHSD activities are affected by changes in sodium and potassium balance and by metabolic acidosis.


METHODS
Renal 11betaHSD activities were measured ex vivo from rats fed normal and high- and low-potassium diets and a low-sodium diet or given 1.5% NH(4)Cl to drink.


RESULTS
Rats maintained on high-potassium and low-sodium diets exhibited 59% (p < 0.01) and 28% (p < 0.05) decreases, respectively, in NAD(+)-dependent renal 11betaHSD activity (relative to rats fed control diet) with no changes in NADP(+)-dependent cortisol oxidation. Short-term (3 day) and longer-term (10 day) metabolic acidosis also decreased NAD(+)-dependent 11betaHSD activity by 50 and 52%, respectively, without affecting NADP(+)-dependent cortisol oxidation. The low-potassium diet had no detectable effect on renal 11betaHSD activities.


CONCLUSIONS
These results suggest that adaptations to a high-potassium or a low-sodium diet and to metabolic acidosis involve decreases in renal 11betaHSD2 activity, enhancing the access of glucocorticoids to renal corticosteroid receptors.
Thompson
A
A
Centre for Nephrology, The Rayne Institute, Royal Free and University College Medical School, London, UK. annat@rfhsm.ac.uk
Bailey
M A
MA
Michael
A E
AE
Unwin
R J
RJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000138:Acidosis / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D011188:Potassium / Q000097:blood / Q000652:urine; D017419:Potassium, Dietary / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage*
D017419:Potassium, Dietary; D012982:Sodium, Dietary; D000643:Ammonium Chloride; D009243:NAD; D000450:Aldosterone; D009249:NADP; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D011188:Potassium