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

Glucocorticoid access to renal corticosteroid receptors is regulated by 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs), converting 11 beta-hydroxyglucocorticoids 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 modulated, upon shifting the electrolyte status land 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 KCI content of standard 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 protein (Western blotting) and mRNA levels (semi-quantitative RT-PCR). In distal tubules, the low KCI diet also had no effect. However, distal tubules of rats fed the high KCl diet showed increased corticosterone 11 beta-oxidation rates (1.6-fold, P<0.01) and 11 beta-HSD2 protein (dr-fold, P < 0.01), whereas 11 beta-HSD1 protein was decreased (no longer detected, P(0.05). Distal tubular 11 beta-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 11 beta-oxidation. This may contribute to the fine-tuning of salt-water homeostasis by the kidney. (C) 1999 Elsevier Science B.V. All rights reserved.