Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Abstract

Liu Y, Singh RJ, Usa K, Netzel BC, Liang M. Renal medullary 11␤-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension. Physiol Genomics 36: 52-58, 2008. First published September 30, 2008 doi:10.1152/physiolgenomics.90283.2008.-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 11␤-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11␤-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13 BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11␤-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-13 BN rats. Knockdown of renal medullary 11␤-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11␤-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13 BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11␤-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11␤-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

Silencing of hypoxia-inducible factor-1α gene attenuates chronic ischemic renal injury in two-kidney, one-clip rats

“…This technique has been shown to effectively deliver DNA into the renal cells without toxicity to the kidney (26,27,41,66,71). The transfection reagent in vivo jetPEI, a polyethylenimine derivative, has been used to successfully deliver DNA into renal cells in vivo in previous studies, including ours (8,29,34,63,69,70). In addition, a combination of ultrasound and different transfection reagents (19,30,40), including polyethylenimine nanoparticles (4), has been shown to significantly enhance the DNA transfection.…”

Dynamic convergence and divergence of renal genomic and biological pathways in protection from Dahl salt-sensitive hypertension

“…This is illustrated by our previous work on molecular networks underlying Dahl salt-sensitive hypertension, which has led to several novel discoveries regarding the overall network (9) and specific components of the network (11,20,22,23).…”

“…Several biological pathways have been found that may contribute to the protection from salt-induced hypertension and/or renal injury observed in the consomic BN strain compared with SS rats. Examples include attenuated oxidative stress (20), reduced local levels of glucocorticoids (11), and improved fumarate metabolism (22,23).…”

11β-Hydroxysteroid Dehydrogenase Type 1 and the Metabolic Syndrome

“…Cortisol and 11 -HSDs have been implicated in hypertension (Anagnostis et al, 2009;Andrews et al, 2003;Campino et al, 2010;Cicala & Mantero, 2010;Edwards et al, 1988;Ferrari, 2010;Franks et al, 2004;Funder et al, 1988;Gathercole & Stewart, 2010;Y. Liu et al, 2008;Malavasi et al, 2010;Millis, 2011;Monder et al, 1989;Morales et al, 2008;Mune et al, 1995;Palermo et al, 2004;Paterson et al, 2004;Quinkler & Stewart, 2003;Raff & Findling, 2003;Stewart et al, 1996;Walker & Andrew, 2006;Walker et al, 1993;Wallerath et al, 1999;White et al, 1997).…”

“…Liu et al showed that suppression of 11 -HSD1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats (Y. Liu et al, 2008). Taking into consideration that diet is one important factor on MetSyn development, it is interesting to mention that in Dahl salt-sensitive hypertensive rats, fed a high-salt diet for 4 weeks, perirenal AT corticosterone concentration and 11 -HSD1 activity as well as GR, 11 -HSD1 and TNF-expression increase when compared with Dahl salt-resistant rats fed the same diet (Usukura et al, 2009).…”