Gene Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 and Type 2 in the Kidneys of Insulin-Dependent Diabetic Rats

—The presence of 11β-hydroxysteroid dehydrogenase (11β-HSD) activity in the kidney has been suggested to be important in the regulation of glucocorticoid-induced disorders of electrolyte balance and the control of blood pressure. To assess the possible effect of 11β-HSD isoforms in diabetes-related hypertension, we measured the mean systolic blood pressure and the 11β-HSD activity and mRNA levels for both 11β-HSD1 and 11β-HSD2 in the kidney of streptozotocin (STZ)-diabetic female rats. Three weeks after injection of STZ (65 mg/kg), the mean systolic blood pressure of diabetic rats was elevated 13.6% above that of normal rats (P <.01). The renal 11β-HSD2 activity and level of mRNA expression were significantly decreased in diabetic rats (P <.01). However, the treatment of rats with STZ did not decrease the levels of renal 11β-HSD1 activity and mRNA expression in diabetic rats. Insulin administered subcutaneously to diabetic rats for 2 weeks completely reversed the decrease in renal 11β-HSD2 activity and gene expression and prevented the elevation in blood pressure in the diabetic rat. These results indicate that alteration of renal 11β-HSD2 activity and gene expression may be primarily responsible for the changes in blood pressure of STZ-diabetic rats after early treatment with insulin.