Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, U.S.A.
Southeast Louisiana Veterans Health Care Systems, New Orleans, LA 70119, U.S.A.
Clin Sci (Lond). 2020 Oct 16;134(19):2535-2547. doi: 10.1042/CS20200483.
The brain renin-angiotensin system (RAS) plays an important role in the regulation of autonomic and neuroendocrine functions, and maintains cardiovascular homeostasis. Ang-II is the major effector molecule of RAS and exerts most of its physiological functions, including blood pressure (BP) regulation, via activation of AT1 receptors. Dysregulation of brain RAS in the central nervous system results in increased Ang-II synthesis that leads to sympathetic outflow and hypertension. Brain angiotensin (Ang) converting enzyme-2 (ACE2) was discovered two decades ago as an RAS component, exhibiting a counter-regulatory role and opposing the adverse cardiovascular effects produced by Ang-II. Studies using synthetic compounds that can sustain the elevation of ACE2 activity or genetically overexpressed ACE2 in specific brain regions found various beneficial effects on cardiovascular function. More recently, ACE2 has been shown to play critical roles in neuro-inflammation, gut dysbiosis and the regulation of stress and anxiety-like behaviors. In the present review, we aim to highlight the anatomical locations and functional implication of brain ACE2 related to its BP regulation via modulation of the sympathetic nervous system and discuss the recent developments and future directions in the ACE2-mediated central cardiovascular regulation.
大脑肾素-血管紧张素系统（RAS）在调节自主神经和神经内分泌功能以及维持心血管稳态方面发挥着重要作用。血管紧张素 II（Ang-II）是 RAS 的主要效应分子，通过激活 AT1 受体发挥其大部分生理功能，包括血压（BP）调节。中枢神经系统中大脑 RAS 的失调导致 Ang-II 合成增加，从而导致交感神经输出增加和高血压。二十年前发现脑血管紧张素（Ang）转换酶-2（ACE2）是 RAS 的一个组成部分，表现出一种代偿性作用，对抗 Ang-II 产生的不良心血管作用。使用可以维持 ACE2 活性升高的合成化合物或在特定脑区过表达 ACE2 的研究发现，对心血管功能有各种有益的影响。最近，ACE2 被证明在神经炎症、肠道菌群失调以及应激和焦虑样行为的调节中起着关键作用。在本综述中，我们旨在强调与通过调节交感神经系统调节 BP 相关的大脑 ACE2 的解剖位置和功能意义，并讨论 ACE2 介导的中枢心血管调节的最新进展和未来方向。
