Regulation of the genes for 11β-hydroxysteroid dehydrogenase type 1 and type 2 in the kidney of the Dahl rat

Background An isoenzyme of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), 11 beta-HSD-2 confers aldosterone specificity on the mineralocorticoid receptor (MR) and is found collocated in renal cortical collecting duct cells with the MR. To investigate whether the salt sensitivity of the Dahl salt-sensitive (S) rat is due to 11 beta-HSD deficiency, we measured 11 beta-HSD-1 and 11 beta-HSD-2 mRNA levels in the kidneys of Dahl-S and Dahl salt-resistant (R) rats. In addition, we studied the effects of gender, age and dietary sodium on expression of mRNA for the two isoforms, S and R rats were placed on low- or high-sodium (HNa) diets and sacrificed after 33 and 115 days. Rat kidney RNA was isolated and 11 beta-HSD-1 and 11 beta-HSD-2 mRNA levels were measured on Northern filter hybridization using isoform-specific probes. Results No strain differences were observed in the mRNA expression of the two isoforms of 11 beta-HSD under any of the experimental conditions. No gender or age differences were observed in 11 beta-HSD-5 mRNA but HNa diet almost doubled 11 beta-HSD-5 mRNA (P < 0.0009), 11 beta-HSD-1 mRNA levels were consistently higher, more than double, in male rats versus females rats (P < 0.0001), and in the 115-day-old rats versus the 33-day-old rats (P < 0.0001). Dietary sodium intake did not affect 11 beta-HSD-1 mRNA levels. Conclusions There is no difference in the expression of the two isoforms of 11 beta-HSD in the kidneys of the S and R rats, which might explain the salt sensitivity and higher blood pressure of the S rat Renal 11 beta-HSD-1 mRNA levels are higher in male than in female rats, and in the older rats of both strains. In the kidney, the 11 beta-HSD-2 gene is regulated by sodium status but is not affected by gender or age. J Hypertens 1999, 17:1089-1093 (C) Lippincott Williams & Wilkins.