Integrative Physiological Aspects of Brain RAS in Hypertension.

The renin-angiotensin system (RAS) plays an important role in modulating cardiovascular function and fluid homeostasis. While the systemic actions of the RAS are widely accepted, the role of the RAS in the brain, its regulation of cardiovascular function, and sympathetic outflow remain controversial. In this report, we discuss the current understanding of central RAS on blood pressure (BP) regulation, in light of recent literature and new experimental techniques. Studies using neuronal or glial-specifc mouse models have allowed for greater understanding into the site-specific expression and role centrally expressed RAS proteins have on BP regulation. While all components of the RAS have been identified in cardiovascular regulatory regions of the brain, their actions may be site specific. In a number of animal models of hypertension, reduction in Ang II-mediated signaling, or upregulation of the central ACE2/Ang 1–7 pathway, has been shown to reduce BP, via a reduction in sympathetic signaling and increase parasympathetic tone, respectively. Emerging evidence also suggests that, in part, the female protective phenotype against hypertension may be due to inceased ACE2 activity within cardiovascular regulatory regions of the brain, potentially mediated by estrogen. Increasing evidence suggests the importance of a central renin-angiotensin pathway, although its localization and the mechanisms involved in its expression and regulation still need to be clarified and more precisely defined. All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

肾素 - 血管紧张素系统（RAS）在调节心血管功能和体液稳态方面起着重要作用。虽然RAS的全身性作用已被广泛接受，但RAS在大脑中的作用、其对心血管功能的调节以及交感神经流出仍然存在争议。在本报告中，我们根据近期文献和新的实验技术，讨论对中枢RAS在血压（BP）调节方面的当前理解。 使用神经元或神经胶质特异性小鼠模型的研究使人们对中枢表达的RAS蛋白在血压调节中的位点特异性表达和作用有了更深入的了解。虽然RAS的所有成分已在大脑的心血管调节区域中被确定，但它们的作用可能具有位点特异性。在许多高血压动物模型中，血管紧张素II介导的信号传导减少，或中枢ACE2/血管紧张素1 - 7通路的上调，已分别显示通过减少交感神经信号传导和增加副交感神经张力来降低血压。新出现的证据还表明，女性对高血压的保护表型可能部分是由于大脑心血管调节区域内ACE2活性增加，可能由雌激素介导。 越来越多的证据表明中枢肾素 - 血管紧张素通路的重要性，尽管其定位以及涉及其表达和调节的机制仍需阐明和更精确地界定。 作者对人类或动物受试者进行的所有已报道的研究/实验均已先前发表，并符合所有适用的伦理标准（包括《赫尔辛基宣言》及其修正案、机构/国家研究委员会标准以及国际/国家/机构指南）。