Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension
Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension
复制标题
DOI：
10.1152/physiolgenomics.90283.2008
复制
发表时间：
2008-12-01
影响因子：
4.6
通讯作者：
Liang, Mingyu
中科院分区：
文献类型：
--
作者：
Liu, Yong;Singh, Ravinder J.;Liang, Mingyu
刘Y，辛格RJ，美国K，Netzel BC，梁M. Dahl盐敏感性高血压患者肾髓质11 β-羟类固醇脱氢酶1型Physiol Genomics 36：52-58，2008.首次发表于2008年9月30日; doi：10.1152/physiolgenomics.90283.2008.- Dahl盐敏感大鼠是一种广泛使用的人类盐敏感型高血压模型。肾脏在Dahl盐敏感性高血压的发病机制中起重要作用，但涉及的分子机制仍然是深入研究的主题。基因表达谱研究表明，11 β-羟基类固醇脱氢酶1型可能是失调的达尔盐敏感大鼠的肾髓质。额外的分析证实，在SS-13（BN）大鼠（一种血压盐敏感性降低的consomic大鼠品系）中，高盐饮食下调了1型11 β-羟基类固醇脱氢酶的肾髓质表达，但在Dahl盐敏感大鼠中没有下调。已知1型11 β-羟基类固醇脱氢酶将无活性的11-脱氢皮质酮转化为活性皮质酮。Dahl盐敏感大鼠的尿皮质酮/11-脱氢皮质酮比值以及尿皮质酮排泄量均高于SS-13（BN）大鼠。用小干扰RNA敲低肾髓质11 β-羟类固醇脱氢酶1型可减弱Dahl盐敏感大鼠盐诱导高血压的早期阶段，并减少皮质酮的尿排泄。敲低11 β-羟基类固醇脱氢酶1型不影响SS-13（BN）大鼠的血压。通过靶向肾髓质11 β-羟基类固醇脱氢酶1型的小发夹RNA实现了盐诱导高血压的长期衰减。总之，我们已经证明，抑制11 β-羟基类固醇脱氢酶1型在肾髓质的表达减弱盐敏感大鼠的盐诱导的高血压。
Liu Y, Singh RJ, Usa K, Netzel BC, Liang M. Renal medullary 11 beta-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 beta-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 beta-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 beta-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 beta-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 beta-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 beta-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11 beta-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.