Laboratorio Interdisciplinar de Investigacao Medica (LIIM), Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston TX, United States.
Curr Med Chem. 2018;25(28):3333-3352. doi: 10.2174/0929867325666180226102358.
The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II.
We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS.
We carried out an extensive literature search in PubMed central.
Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis.
Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.
肾素-血管紧张素系统（RAS）是心血管和肾脏内稳态的关键调节剂，但在调节中枢神经系统（CNS）的生理功能方面也发挥着重要作用。RAS 的作用经典地描述为通过血管紧张素（Ang）II 经由血管紧张素 1 型（AT1）受体介导。然而，由血管紧张素转换酶 2（ACE2）、Ang-（1-7）和 Mas 受体形成的 RAS 的另一个分支，由于其重要的生理作用，通常与 Ang II 产生的经典作用相平衡，因此一直是研究的对象。
我们旨在提供 RAS，特别是 Ang-（1-7）在大脑中产生的作用的概述。我们还旨在讨论调节 RAS 治疗神经精神疾病的潜在治疗方法。
我们在 PubMed Central 中进行了广泛的文献检索。
在大脑中，Ang-（1-7）通过作用于控制心血管功能的区域来参与血压的调节。与 Ang II 相反，Ang-（1-7）可提高压力反射敏感性，并在下丘脑去甲肾上腺素能神经传递中发挥抑制作用。Ang-（1-7）不仅发挥与血压调节相关的作用，而且还作为 RAS 的神经保护成分发挥作用，例如，通过减少脑梗死面积、炎症、氧化应激和神经元凋亡。
临床前证据支持 ACE2/Ang-（1-7）/Mas 受体轴在几种神经精神疾病中的重要作用，包括应激相关和情绪障碍、脑血管缺血和出血性病变以及神经退行性疾病。然而，关于 ACE2/Ang-（1-7）/Mas 受体轴在人类中枢神经系统中的数据非常有限。
