Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin
Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin
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DOI：
10.1681/asn.2017030243
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发表时间：
2018-01-01
影响因子：
13.6
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
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作者：
Hirohama, Daigoro;Ayuzawa, Nobuhiro;Fujita, Toshiro
肾素-血管紧张素-醛固酮系统在血容量不足时的体液平衡和血压控制中起重要作用。饮食限制盐升高循环血管紧张素II（AngII）和醛固酮水平，增加β-嵌入细胞中Cl-/HCO 3-交换器pendrin和远曲小管中Na+-Cl-协同转运蛋白（NCC）的水平。然而，AngII和醛固酮在调节这些水平中的独立作用仍不清楚。在接受低盐饮食或AngII输注的C57 BL/6 J小鼠中，我们评估了pendrin和NCC的膜蛋白丰度;评估了盐皮质激素受体的磷酸化，盐皮质激素受体选择性抑制嵌入细胞中的醛固酮结合;并通过无线电遥测法测量了pendrin敲除小鼠和野生型小鼠的血压。低盐饮食或血管紧张素II输注上调NCC和pendrin水平，降低β-嵌入细胞中盐皮质激素受体的磷酸化，并增加血浆醛固酮水平。值得注意的是，低盐饮食没有改变野生型小鼠的血压，但显着降低pendrin敲除小鼠的血压。为了分析血管紧张素II和醛固酮的作用，我们对小鼠进行了肾上腺切除术，以从循环中去除醛固酮。在肾上腺切除小鼠，血管紧张素II输注再次上调NCC的表达，但不影响pendrin的表达，尽管盐皮质激素受体的磷酸化水平降低。相比之下，血管紧张素II和醛固酮共同管理显着升高肾上腺切除小鼠pendrin水平。我们的研究结果表明，醛固酮是必要的血管紧张素II诱导pendrin上调，并建议，pendrin有助于维持正常的BP与NCC合作期间激活的reninangiotensin-醛固酮系统的饮食限盐。
The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl-/HCO3- exchanger pendrin in beta-intercalated cells and the Na+-Cl- cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin andNCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrinknockout and wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin levels, decreased the phosphorylation of mineralocorticoid receptor in beta-intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrinknockout mice. To dissect the roles of AngII and aldosterone, we performed adrenalectomies inmice to remove aldosterone from the circulation. In adrenalectomized mice, AngII infusion again upregulated NCC expression, but did not affect pendrin expression despite the decreased phosphorylation of mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration markedly elevated pendrin levels in adrenalectomized mice. Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to the maintenance of normal BP in cooperation with NCC during activation of the reninangiotensin- aldosterone system by dietary salt restriction.