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
11beta-hydroxysteroid dehydrogenase (11beta-HSD). There are two
isoforms of 11beta-HSD (11beta-HSD1 and 11beta-HSD2). Deficiency or inhibition of
11beta-HSD2 causes
sodium retention and
hypertension. In the present study we measured the activity of hepatic and kidney
11beta-HSD1 in Dahl-S and R rats before and after the development of
hypertension. The activity of
11beta-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, 11beta-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 AI/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 11beta-HSD1 activity at 6 weeks of age and lower kidney 11beta-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 11beta-HSD1 may play a role in the
salt sensitivity and development of
hypertension in the Dahl-S rat.