Aldosterone-independent regulation of the epithelial Na+ channel (ENaC) by vasopressin in adrenalectomized mice
Aldosterone-independent regulation of the epithelial Na+ channel (ENaC) by vasopressin in adrenalectomized mice
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DOI：
10.1073/pnas.1201978109
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发表时间：
2012-06-19
影响因子：
11.1
通讯作者：
Stockand, James D.
中科院分区：
文献类型：
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作者：
Mironova, Elena;Bugaj, Vladislav;Stockand, James D.
在保护钠平衡和血压的过程中，肾素-血管紧张素-醛固酮系统负反馈调节肾素敏感远端肾单位(ASDN)上皮细胞的钠离子通道(ENaC)。我们在这里测试醛固酮是否对ASDN中ENaC的表达和活性是必要的和充分的。令人惊讶的是，ENaC在肾上腺切除(ADX)小鼠中的表达和活性都很强。在对照组和ADX小鼠中，外源性矿物皮质激素同样能很好地促进ENaC活性。与对照组相比，ADX组小鼠血浆[AVP]显著升高。加压素(AVP)刺激ENaC。抑制V-2 AVP受体可抑制ADX小鼠的ENaC活性。缺乏醛固酮和AVP释放增加损害了ADX小鼠ENaC对钠摄入量变化的正常反馈调节。这些结果表明，醛固酮对ASDN中的ENaC活动是充分的，但不是必需的。AVP非依赖于醛固酮的刺激使ENaC在ASDN中的作用从保护Na+平衡转变为促进水分重吸收。这种对ENaC的刺激可能导致肾上腺功能不全的低钠血症。
The epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) is under negative-feedback regulation by the renin-angiotensin-aldosterone system in protection of sodium balance and blood pressure. We test here whether aldosterone is necessary and sufficient for ENaC expression and activity in the ASDN. Surprisingly, ENaC expression and activity are robust in adrenalectomized (Adx) mice. Exogenous mineralocorticoid increases ENaC activity equally well in control and Adx mice. Plasma [AVP] is significantly elevated in Adx vs. control mice. Vasopressin (AVP) stimulates ENaC. Inhibition of the V-2 AVP receptor represses ENaC activity in Adx mice. The absence of aldosterone combined with elevated AVP release compromises normal feedback regulation of ENaC in Adx mice in response to changes in sodium intake. These results demonstrate that aldosterone is sufficient but not necessary for ENaC activity in the ASDN. Aldosterone-independent stimulation by AVP shifts the role of ENaC in the ASDN from protecting Na+ balance to promoting water reabsorption. This stimulation of ENaC likely contributes to the hyponatremia of adrenal insufficiency.