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高钾饮食调节血压的肾脏机制

孟桂林¹, 孟欣欣¹, 谷瑞民², 王明晓^1,*

¹遵义医科大学珠海校区生理学教研室，珠海 519040；²哈尔滨医科大学药学院，哈尔滨 150081

摘要

高血压是引起心血管疾病、脑卒中和肾功能衰竭最强风险因素之一。日常生活方式和饮食是调节血压的重要因素。高血压患者可通过增加体育锻炼、减少酒和钠的摄取以及戒烟等方式降低血压。除此之外，饮食中增加钾含量丰富的食物也有益于血压的控制。慢性肾脏疾病患者通常伴有高血压，说明肾脏是维持血压平衡的重要器官。在肾脏，高钾饮食降低血压的效应与肾小管对NaCl的重吸收降低、尿钠排泄增加有关。在这个过程中，肾脏远端小管(distal convoluted tubule, DCT)细胞膜上的钠-氯同向转运体(sodium-chloride cotransporter, NCC)发挥至关重要作用。在DCT细胞，NCC的激活与对细胞内Cl−敏感的丝氨酸/苏氨酸蛋白激酶(with-no-lysine kinases, WNKs)及下游Ste20相关的富含脯氨酸-丙氨酸激酶(Ste20-related proline-alanine-rich kinase, SPAK)和氧化应激反应激酶1 (oxidative stress-responsive kinase 1, OSR1)相关，其中WNK4是WNKs家族决定NCC活性的关键激酶。当细胞内Cl−浓度升高时，WNK4-SPAK/OSR1途径被抑制，NCC蛋白活性及磷酸化水平降低；相反，当细胞内Cl−浓度降低时，NCC活性增强。根据我们前期研究的结果，高钾饮食能够降低DCT细胞管周膜Kir4.1/5.1钾通道活性，引起细胞膜去极化，导致细胞内Cl−浓度增高，抑制WNK4-SPAK/OSR1-NCC通路，降低NCC活性。本综述对上述高钾调节DCT细胞膜上的转运体活性及机制进行总结，以利于诠释高钾饮食降低血压的肾脏机制。

关键词： 高血压; 高钾饮食; 远曲小管; 钠-氯同向转运体

The mechanism of blood pressure regulation by high potassium diet in the kidney

MENG Gui-Lin¹, MENG Xin-Xin¹, GU Rui-Min², WANG Ming-Xiao^1,*

¹Department of Physiology, Zhuhai Campus of Zunyi Medical University, Zhuhai 519040, China；²Department of Pharmacology, Harbin Medical University, Harbin 150081, China

Abstract

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl−]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl−]i. High [Cl−]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.

Key words: Hypertension; high potassium diet; distal convoluted tubule; sodium-chloride cotransporter

收稿日期：　　录用日期：

通讯作者：王明晓　　E-mail: wmxzyzh@163.com

DOI: 10.13294/j.aps.2021.0066

引用本文：

孟桂林, 孟欣欣, 谷瑞民, 王明晓. 高钾饮食调节血压的肾脏机制[J]. 生理学报 2022; 74 (1): 110-116.

MENG Gui-Lin, MENG Xin-Xin, GU Rui-Min, WANG Ming-Xiao. The mechanism of blood pressure regulation by high potassium diet in the kidney. Acta Physiol Sin 2022; 74 (1): 110-116 (in Chinese with English abstract).