A current view of brain renin-angiotensin system: Is the (pro)renin receptor the missing link?
A current view of brain renin-angiotensin system: Is the (pro)renin receptor the missing link?
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DOI：
10.1016/j.pharmthera.2009.07.007
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发表时间：
2010-01
影响因子：
13.5
通讯作者：
Raizada MK
中科院分区：
文献类型：
--
作者：
Cuadra AE;Shan Z;Sumners C;Raizada MK
肾素血管紧张素系统(RAS)在大脑中起着调节血压(BP)的核心作用。这种作用包括调节交感神经活动(SNA)，调节血管张力，调节对电解质和液体稳态起关键作用的神经激素的分泌，以及通过影响增加盐和水摄入量的行为过程。几十年的研究表明，血管紧张素II(Ang II)是RAS的主要生物活性产物，它主要通过位于下丘脑和脑干控制中心的Ang II 1型受体(AT1R)来介导这些作用。然而，大脑RAS功能的机制一直受到质疑，这在很大程度上是由于中枢神经系统中限速酶肾素的低表达水平。在心脏、肾小管和血管细胞中已观察到组织定位的RAS。研究还提出了脑内局部RAS功能的假说，因此Ang II可以旁分泌的方式影响神经元的活动。最近发现的(PRO)肾素受体(PRR)可能在这一机制中起关键作用，因为它为局部RAS活性隔离肾素和原肾素。因此，PRR可以潜在地减轻大脑中低水平的肾素表达，以传播Ang II的作用。在这篇综述中，我们考察了大脑中各种RAS组分的调节、表达和功能特性，特别是PRR在血压调节和高血压中可能扮演的不同角色。
The renin angiotensin system (RAS) plays a central role in the brain to regulate blood pressure (BP). This role includes the modulation of sympathetic nerve activity (SNA) that regulates vascular tone, the regulation of secretion of neurohormones that have a critical role in electrolyte and fluid homeostasis, and by influencing behavioral processes to increase salt and water intake. Based on decades of research it is clear that angiotensin II (Ang II), the major bioactive product of the RAS, mediates these actions largely via its Ang II type 1 receptor (AT1R), located within hypothalamic and brainstem control centers. However, the mechanisms of brain RAS function have been questioned, due in large part to low expression levels of the rate limiting enzyme renin within the central nervous system. Tissue localized RAS has been observed in heart, kidney tubules and vascular cells. Studies have also given rise to the hypothesis for localized RAS function within the brain, so that Ang II can act in a paracrine manner to influence neuronal activity. The recently discovered (pro)renin receptor (PRR) may be key in this mechanism as it serves to sequester renin and prorenin for localized RAS activity. Thus, the PRR can potentially mitigate the low levels of renin expression in the brain to propagate Ang II action. In this review we examine the regulation, expression and functional properties of the various RAS components in the brain with particular focus on the different roles that PRR may have in BP regulation and hypertension.
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影响因子：
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