Renal 11β-hydroxysteroid dehydrogenase in genetically salt-sensitive hypertensive rats

Renal 11 beta-hydroxysteroid dehydrogenase II (11 beta-HSDII) converts glucocorticoids into inactive metabolites and plays an important role in controlling blood pressure and sodium retention. To examine whether this enzyme may be involved in the pathophysiology of salt-sensitive hypertension, we determined 11 beta-HSDII activity and mRNA levels in the blood vessel and kidney of Dahl Iwai salt-sensitive (DS) rats and Dahl Iwai salt-resistant (DR) rats. Urinary free corticosterone:free Il-dehydrocorticosterone ratio was measured to estimate renal 11 beta-HSD activity. Vascular 11 beta-HSDII activity was expressed as percent conversion of [H-3]corticosterone to [H-3]11-dehydrocorticosterone in homogenized mesenteric arteries. 11 beta-HSDII mRNA was estimated with the use of competitive polymerase chain reaction (PCR), Renal 11 beta-HSDII activity and mRNA levels were significantly decreased in 8- and 12-week-old high salt DS rats compared with DR, Sprague-Dawley (SD), or low salt DS rats of the same age. Decreased 11 beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8- and 12-week-old high salt DS rats. Urinary excretion of 11 beta-HSDII inhibitory factors was measured by inhibition of enzyme activity in microsomes from human kidney. The urinary inhibitors were significantly increased in 8- and 12-week-old high salt DS rats compared with DR, SD, or low salt DS rats of the same age. There were no significant differences in 11 beta-HSDII activity and mRNA levels in mesenteric arteries and kidney or in urinary inhibitors between 4-week-old DS, DR, and SD rats. These results indicate that 11 beta-HSDII may play a role in salt sensitivity and development of hypertension in the DS rat.