11β-Hydroxysteroid Dehydrogenase in the Dahl Rat

Dahl salt sensitive (Dahl-S) rats develop hypertension soon after birth. The cause of the increased salt-sensitivity in the Dahl-S rat is unknown. The mineralocorticoid specificity of the kidney receptor is conferred by the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD). There are two isoforms of 11β-HSD (11β-HSD1 and 11β-HSD2). Deficiency or inhibition of 11β-HSD2 causes sodium retention and hypertension. In the present study we measured the activity of hepatic and kidney 11β-HSD1 in Dahl-S and R rats before and after the development of hypertension. The activity of 11β-HSD1 in the liver was lower in the Dahl-S rats at 6 weeks of age (S = 8.01 ± 0.89 v R = 11.91 ± 0.84 nmol/mg protein/10 min (P< .02) but there was no difference at 10 weeks. In contrast, 11β-HSD1 in the kidney was not different at 6 weeks but it was significantly lower in the Dahl-S rats at 10 weeks (S = 0.91 ± 0.04 v R = 1.12 ± 0.01 nmol/mg protein/10 min (P< .001). Plasma renin concentration was lower at 6 (6w) and 10 weeks (10w) in the Dahl-S rats: S-6w = 4.2 ± 0.4 versus R-6W = 6.3 ± 0.8 ng angiotensin I (AI)/mL/h (P< .04) and S-10w = 6.4 ± 0.7 versus R-10w = 10 ± 0.9 ng Al/mL/h (P< .009). Plasma aldosterone and corticosterone were not different between the two strains. Systolic blood pressure (SBP) in the Dahl-S rats was 124 ± 3 mm Hg at 6 weeks and 241 ± 6 mm Hg at 10 weeks (P< .001). SBP in the Dahl-R rats was 113 ± 5 mm Hg at 6 weeks and 143 ± 4 mm Hg at 10 weeks. In conclusion, Dahl-S rats have lower hepatic 11β-HSD1 activity at 6 weeks of age and lower kidney 11β-HSD1 at 10 weeks of age compared with Dahl-R rats of the same age. These findings suggest that diminished activity of both liver and kidney 11β-HSD1 may play a role in the salt sensitivity and development of hypertension in the Dahl-S rat.