Aldosterone-induced abnormal regulation of ENaC and SGK1 in Dahl salt-sensitive rat
Aldosterone-induced abnormal regulation of ENaC and SGK1 in Dahl salt-sensitive rat
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DOI：
10.1016/j.bbrc.2005.12.194
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发表时间：
2006-03-10
影响因子：
3.1
通讯作者：
Marunaka, Y
中科院分区：
文献类型：
--
作者：
Aoi, W;Niisato, N;Marunaka, Y
醛固酮在控制体内矿物质平衡方面起着至关重要的作用。已有报道，醛固酮通过刺激上皮性钠离子通道(ENaC)的表达，并激活ENaC调节的蛋白激酶、血清和糖皮质激素调节的蛋白激酶1(SGK1)，从而促进肾脏对Na+的重吸收。然而，尚不清楚在异常的盐敏感性高血压条件下，醛固酮是否对ENaC和SGK1有刺激作用。为了阐明这一点，我们研究了醛固酮如何调节高盐饮食高血压Dahl盐敏感(DS)大鼠ENaC和SGK1的表达。给去肾上腺的DS和Dahl耐盐(DR)大鼠皮下注射醛固酮(1.5 mg/kg体重)6h后，从肾脏提取RNA和蛋白质。与DR大鼠不同，醛固酮降低了DS大鼠β-和γ-ENaC的mRNA表达，而增加了类似于DR的DS大鼠α-ENaC的mRNA表达。此外，我们还发现，醛固酮提高了DR大鼠SGK1的表达，但对DS大鼠的SGK1表达无影响。这些观察结果表明，盐敏性高血压大鼠的ENaC和SGKI受到醛固酮的异常调节，提示醛固酮调节紊乱可能是引起盐敏性高血压的因素之一。(C)2006 Elsevier Inc.保留所有权利。
Aldosterone plays a crucial role in controlling mineral balance in our body. The mechanism of aldosterone has been reported to elevate renal Na+ reabsorption by stimulating expression of epithelial Na+ channel (ENaC) and also activate an ENaC-regulating protein kinase, serum and glucocorticoid-regulated kinase 1 (SGK1). However, it is unknown whether aldosterone shows its stimulatory action on ENaC and SGK1 under an abnormal, salt-sensitive hypertensive condition. To clarify this point, we studied how aldosterone regulates expression of ENaC and SGK1 in Dahl salt-sensitive (DS) rat that shows hypertension with high salt diet. RNA and protein were extracted from the kidney 6 h after application of aldosterone (1.5 mg/kg body weight) subcutaneously injected into adrenalectomized DS and Dahl salt-resistant (DR) rats. Aldosterone decreased mRNA expression of beta- and gamma-ENaC in DS rat unlike DR rat, while aldosterone increased alpha-ENaC mRNA expression in DS rat similar to DR rat. Further, we found that aldosterone elevated SGK1 expression in DR rat, but not in DS rat. These observations indicate that ENaC and SGKI are abnormally regulated by aldosterone in salt-sensitive hypertensive rats, suggesting that disturbance of the aldosterone regulation would be one of factors causing salt-sensitive hypertension. (c) 2006 Elsevier Inc. All rights reserved.