High dietary potassium chloride intake augments rat renal mineralocorticoid receptor selectivity via 11beta-hydroxysteroid dehydrogenase.
Glucocorticoid access to renal corticosteroid receptors is regulated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), converting 11beta-hydroxyglucocorticoids into inactive 11-ketones. This mechanism plays a key role in maintaining normal salt-water homeostasis and blood pressure. To study whether renal cortical proximal and distal tubular 11beta-HSDs are modulated, upon shifting the electrolyte status (and may thereby contribute to adjusting the salt-water homeostasis), rats were treated for 14 days with diets with low (0.058 w/w%), normal (0.58%, which is the KCl content of standard European laboratory rat food) or high (5.8%) potassium chloride content. In proximal tubules, dietary KCl had no effect regarding corticosterone 11beta-oxidation in intact cells as well as 11beta-HSD1 and 11beta-HSD2 protein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In distal tubules, the low KCl diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11beta-oxidation rates (1.6-fold, P<0.01) and 11beta-HSD2 protein (4-fold, P<0.01), whereas 11beta-HSD1 protein was decreased (no longer detected, P<0.05). Distal tubular 11beta-HSD mRNA levels were not changed upon dietary treatment. Our results suggest that upon dietary KCl loading distal tubular mineralocorticoid receptor selectivity for aldosterone is increased because of enhanced corticosterone 11beta-oxidation. This may contribute to the fine-tuning of salt-water homeostasis by the kidney.
Hermans
J J
JJ
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, University of Maastricht, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. r.hermans@farmaco.unimaas.nl
Fischer
M A
MA
Schiffers
P M
PM
Struijker-Boudier
H A
HA
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D011189:Potassium Chloride / Q000008:administration & dosage; D017419:Potassium, Dietary / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D007527:Isoenzymes; D017419:Potassium, Dietary; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D011189:Potassium Chloride; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone