High dietary potassium chloride intake augments rat renal mineralocorticoid receptor selectivity via 11 beta-hydroxysteroid dehydrogenase

Glucocorticoid access to renal corticosteroid receptors is regulated by 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), converting 11 beta-hydro xyglucocorticoids into inactive Il-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 11 beta-HSDs are modulat ed, upon shifting the electrolyte status land may thereby contribute to adj usting the salt-water homeostasis), rats were treated for 14 days with diet s with low (0.058 w/w%), normal (0.58%, which is the KCI content of standar d European laboratory fat food) or high (5.8%) potassium chloride content. In proximal tubules, dietary KCI had no effect regarding corticosterone 11 beta-oxidation in intact cells as well as 11 beta-HSD1 and 11 beta-HSD2 pro tein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In dist al tubules, the low KCI diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11 beta-oxidati on rates (1.6-fold, P<0.01) and 11 beta-HSD2 protein (dr-fold, P < 0.01), w hereas 11 beta-HSD1 protein was decreased (no longer detected, P(0.05). Dis tal tubular 11 beta-HSD mRNA levels were not changed upon dietary treatment . Our results suggest that upon dietary KCl loading distal tubular mineralo corticoid receptor selectivity for aldosterone is increased because of enha nced corticosterone 11 beta-oxidation. This may contribute to the fine-tuni ng of salt-water homeostasis by the kidney. (C) 1999 Elsevier Science B.V. All rights reserved.