The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.
The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain.
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DOI：
10.1038/hr.2011.105
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发表时间：
2011-11
影响因子：
5.4
通讯作者：
Nishimura, Masato
中科院分区：
文献类型：
--
作者：
Takahashi, Hakuo;Yoshika, Masamichi;Komiyama, Yutaka;Nishimura, Masato
关键词：
中枢神经系统通过调节交感和副交感神经系统、垂体激素释放和压力感受器反射，在调节循环系统中起着关键作用。20年前，人们在下丘脑的核中发现了类似地高辛和哇巴因的免疫反应物质。这些因素似乎定位于室旁核和视上核，以及室周器官的神经纤维，并被认为影响电解质平衡和血压。这些物质的周转率随着钠摄入量的增加而增加。由于哇巴因脑室注射通过交感神经激活而升高血压，一种内源性洋地黄样因子(EDLF)被认为调节大脑中与心血管系统相关的功能，特别是在钠负荷后。主要在大鼠身上进行的实验表明，哇巴因在大脑中的作用机制涉及钠离子、上皮钠通道(ENaCs)和肾素-血管紧张素-醛固酮系统(RAAS)，所有这些都受到钠负荷的影响。喂食高钠饮食的大鼠脑脊液中的钠水平升高，这会激活ENaCs。激活的ENaCs和/或增加的神经元内钠激活RAAS；这会在大脑中释放EDLF，激活交感神经系统。RAAS促进大脑中的氧化应激，进一步激活RAAS并增加交感神经流出。血管紧张素II和外周来源的醛固酮在大脑中作用，激活这种级联反应，增加交感神经流出，导致高血压。因此，脑Na+-ENaC-RAAS-EDLF轴激活交感神经流出，在高血压和继发性高血压中起关键作用。这份报告概述了高血压的主要机制，并讨论了抗高血压药物的使用。
The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents.
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