Central role for ENaC in development of hypertension
Central role for ENaC in development of hypertension
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DOI：
10.1681/asn.2005050460
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发表时间：
2005-11-01
影响因子：
13.6
通讯作者：
Pratt, JH
中科院分区：
文献类型：
--
作者：
Pratt, JH
皮质集合管上皮Na+通道（ENaC）的Na+重吸收提供了肾脏对Na+平衡的最终调节，没有进一步的下游Na+转运系统。这一事实加上ENaC对醛固酮的反应性，其传递与Na+平衡状态成反比的刺激，将ENaC置于影响高血压风险的关键位置。尽管已经鉴定出ENaC亚基的几种分子变体，但尚未一致证明任何变体与高血压相关。更令人信服的是，ENaC活性不能完全适应肾单位其他部位Na+重吸收的增加，因为不适当升高的醛固酮水平会过度刺激。高血压的维持可能依赖于ENaC的其他证据来自于观察到的对ENaC抑制剂治疗高血压个体的反应。描述了一项临床试验，其中黑人高血压患者对传统治疗没有完全反应，给予阿米洛利、螺内酯、两种药物的组合或安慰剂。用ENaC的活性抑制剂中的任一种治疗导致BP的实质性改善。总之，迄今为止的证据支持ENaC增加Na+转运可能是盐依赖型高血压的常见和必要组成部分的概念。
Na+ reabsorption by the epithelial Na+ channel (ENaC) in cortical collecting duct provides the final renal adjustment to Na+ balance, there being no further downstream Na+ transport system. This fact coupled with the responsiveness of ENaC to aldosterone, which conveys stimulation inversely proportional to the state of Na+ balance, places ENaC in a pivotal position to influence the risk for hypertension. Although several molecular variants of ENaC subunits have been identified, there has been no consistent demonstration of an association of any of the variants with hypertension. More compelling is the notion that ENaC activity does not fully adjust to an increase in Na+ reabsorption occurring elsewhere in the nephron, there being overstimulation by inappropriately elevated aldosterone levels. Additional evidence that the maintenance of hypertension can be dependent on ENaC is derived from the observed responses to the treatment of hypertensive individuals with inhibitors of ENaC. Described is a clinical trial in which black hypertensive individuals who did not fully respond to more traditional therapy were given amiloride, spironolactone, a combination of the two drugs, or placebo. Treatment with either of the active inhibitors of ENaC resulted in a substantial improvement in BP. In conclusion, evidence to date is supportive of the concept that an increase in Na+ transport by ENaC may be a common and requisite component of salt-dependent forms of hypertension.