PG-90283-2008.R2 1 Renal Medullary 11β-Hydroxysteroid Dehydrogenase Type 1 in

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dys-regulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt-sensitivity, but not in Dahl salt-sensitive rats. 11β-hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinar