Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone
Angiotensin II induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter independent of aldosterone
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DOI：
10.1038/ki.2010.290
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发表时间：
2011-01-01
影响因子：
19.6
通讯作者：
Hoorn, Ewout J.
中科院分区：
文献类型：
--
作者：
van der Lubbe, Nils;Lim, Christina H.;Hoorn, Ewout J.
我们在此研究了血管紧张素 II 和醛固酮在调节远曲小管氯化钠协同转运蛋白 (NCC) 中的独立作用。我们切除了三只实验组大鼠和一组对照组大鼠的肾上腺。手术后，实验组接受高生理剂量的醛固酮、非升压药或升压剂量的血管紧张素 II 治疗，持续 8 天。与对照组相比，醛固酮和两种剂量的血管紧张素 II 均降低了钠排泄，并显着增加了质膜中 NCC 的丰度。只有血管紧张素II的升压剂量才会引起高血压。噻嗪类药物可抑制血管紧张素 II 非升压药剂量引起的钠潴留。醛固酮和非升压剂量的血管紧张素 II 均显着增加了 NCC 苏氨酸 53 的磷酸化，并且还增加了 STE20/SPS1 相关的富含脯氨酸丙氨酸激酶 (SPAK) 的细胞内丰度。在 NCC 活性的其他调节剂中没有发现差异，例如氧化应激反应蛋白 1 型或不含赖氨酸激酶 4。因此，我们的体内研究表明，醛固酮和血管紧张素 II 独立增加肾上腺切除术中 NCC 的丰度和磷酸化；效应可能是由 SPAK 介导的。这些结果可以部分解释肾脏钠排泄的激素控制和几种高血压的病理生理学。肾脏国际 (2011) 79, 66-76; doi：10.1038/ki.2010.290； 2010 年 8 月 18 日在线发布
We studied here the independent roles of angiotensin II and aldosterone in regulating the sodium chloride cotransporter (NCC) of the distal convoluted tubule. We adrenalectomized three experimental and one control group of rats. Following surgery, the experimental groups were treated with either a high physiological dose of aldosterone, a non-pressor, or a pressor dose of angiotensin II for 8 days. Aldosterone and both doses of angiotensin II lowered sodium excretion and significantly increased the abundance of NCC in the plasma membrane compared with the control. Only the pressor dose of angiotensin II caused hypertension. Thiazides inhibited the sodium retention induced by the angiotensin II non-pressor dose. Both aldosterone and the non-pressor dose of angiotensin II significantly increased phosphorylation of NCC at threonine-53 and also increased the intracellular abundance of STE20/SPS1-related, proline alanine-rich kinase (SPAK). No differences were found in other modulators of NCC activity such as oxidative stress responsive protein type 1 or with-no-lysine kinase 4. Thus, our in vivo study shows that aldosterone and angiotensin II independently increase the abundance and phosphorylation of NCC in the setting of adrenalectomy; effects are likely mediated by SPAK. These results may explain, in part, the hormonal control of renal sodium excretion and the pathophysiology of several forms of hypertension. Kidney International (2011) 79, 66-76; doi: 10.1038/ki.2010.290; published online 18 August 2010