Aberrant ENaC activation in Dahl salt-sensitive rats
Aberrant ENaC activation in Dahl salt-sensitive rats
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DOI：
10.1097/hjh.0b013e32832c7d23
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Tomita, Kimio
中科院分区：
文献类型：
--
作者：
Kakizoe, Yutaka;Kitamura, Kenichiro;Tomita, Kimio
背景：上皮性钠通道(ENaC)通过调节肾脏对钠的重吸收，在血压调节中发挥重要作用。高盐饮食导致Dahl盐敏感大鼠发生严重高血压，尽管血浆醛固酮浓度(PAC)受到抑制，但高盐饮食仍可异常刺激Dahl盐敏感大鼠肾脏ENaC基因的表达。并检测了阿米洛利(5 mg/kg/d)和依普利酮(0.125%饲料)对Dahl盐敏感大鼠血压和肾脏损伤的影响。结果：Dahl盐敏感大鼠在高盐饮食治疗4周后出现高血压和肾损害。高盐饮食对Dahl盐敏感大鼠的PAC和肾脏醛固酮含量均有抑制作用，但β和γENaC基因表达和蛋白丰度均显著增加。与低盐组或高盐饮食的Dahl耐盐大鼠相比，高盐饮食的Dahl盐敏感大鼠的γENaC分子量从85 kDa增加到70 kDa，这是ENaC激活的标志。阿米洛利治疗4周后，高盐饮食的Dahl盐敏感大鼠的高血压和肾脏损伤明显改善，提示ENaC的异常激活不依赖于醛固酮。结论：ENaC的异常表达和激活可能是Dahl盐敏感大鼠发生盐敏感性高血压和器官损害的潜在机制之一，提示阿米洛利对ENaC过度激活的盐敏感性高血压有治疗作用。J Hyperten 27：1679-1689(C)2009沃尔特斯·克鲁沃健康垂直酒吧Lippincott Williams&Wilkins。
Background: The epithelial sodium channel (ENaC) plays an important role in the regulation of blood pressure by modulating Na reabsorption in the kidney. Dahl salt-sensitive rats on high-salt diet develop severe hypertension, and high-salt diet has been reported to stimulate ENaC mRNA expression in the kidney abnormally in Dahl salt-sensitive rats despite a suppressed plasma aldosterone concentration (PAC).Methods: We investigated the effect of high-salt diet on ENaC protein expression in Dahl salt-resistant and Dahl salt-sensitive rats, and examined the effect of amiloride (5 mg/kg per day) and eplerenone (0.125% diet) on blood pressure and renal injury in Dahl salt-sensitive rats.Results: Dahl salt-sensitive rats developed hypertension and renal damage following 4 weeks of treatment with high-salt diet. Although PAC and kidney aldosterone content were all suppressed by the high-salt diet in Dahl salt-sensitive rats, both beta and gamma ENaC mRNA expression and protein abundance were significantly increased. The molecular weight shift of gamma ENaC from 85 to 70 kDa, an indication of ENaC activation, was clearly increased in Dahl salt-sensitive rats on high-salt diet compared with the low-salt group or Dahl salt-resistant rats on high-salt diet. Four weeks of treatment with amiloride, but not eplerenone, significantly ameliorated hypertension and kidney injury in Dahl salt-sensitive rats fed high-salt diet, suggesting aberrant aldosterone-independent activation of ENaC.Conclusion: These results suggest that inappropriate expression and activation of ENaC could be one of the underlying mechanisms by which Dahl salt-sensitive rats develop salt-sensitive hypertension and organ damage, and indicate a therapeutic benefit of amiloride in salt-sensitive hypertension where ENaC is excessively activated. J Hypertens 27: 1679-1689 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.