Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.
Recent Updates on the Proximal Tubule Renin-Angiotensin System in Angiotensin II-Dependent Hypertension.
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DOI：
10.1007/s11906-016-0668-z
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发表时间：
2016-08
影响因子：
5.6
通讯作者：
Zhuo JL
中科院分区：
文献类型：
--
作者：
Li XC;Zhuo JL
众所周知，肾素-血管紧张素系统(RAS)不仅以循环、旁分泌(细胞对细胞)的形式存在，也以细胞内(细胞内)的形式存在。然而，在肾脏中，很难分析循环RAS和肾内RAS在近端肾小管Na+重吸收和高血压的生理调节中的各自作用。在这里，我们回顾最近的研究，以提供这一研究领域的最新进展，重点是血管紧张素II(Ang II)诱导的高血压中近端肾小管RAS的作用。对现有证据的仔细分析支持这一假设，即局部合成或形成以及AT1(AT1a)受体和/或megalin介导的血管紧张素原(AGT)、Ang I和Ang II的摄取导致肾脏近端小管中Ang II的高水平。在生理条件下，几乎所有RAS的主要成分，包括AGT、前肾素、肾素、Ang I和Ang II都会被肾小球过滤，并被近端小管摄取。在Ang II依赖型高血压中，AGT、前肾素和(Pro)肾素受体以及血管紧张素转换酶(ACE)在肾脏中的表达上调而不是下调。此外，高血压还会损害肾小球滤过屏障，使循环中的AGT、前肾素、肾素、血管紧张素转换酶I和血管紧张素II的滤过率增加，并使它们在近端小管的摄取增加。总之，通过AT1(AT1a)受体和Na+/H+交换器3的激活，局部Ang II的形成和近端小管对循环Ang II的摄取增加，可能为促进Na+滞留和Ang II诱导的高血压的发展提供了强大的前馈机制。
It is well recognized that the renin-angiotensin system (RAS) exists not only as circulating, paracrine (cell to cell), but also intracrine (intracellular) system. In the kidney, however, it is difficult to dissect the respective contributions of circulating RAS versus intrarenal RAS to the physiological regulation of proximal tubular Na+ reabsorption and hypertension. Here, we review recent studies to provide an update in this research field with a focus on the proximal tubular RAS in angiotensin II (ANG II)-induced hypertension. Careful analysis of available evidence supports the hypothesis that both local synthesis or formation and AT1 (AT1a) receptor-and/or megalin-mediated uptake of angiotensinogen (AGT), ANG I and ANG II contribute to high levels of ANG II in the proximal tubules of the kidney. Under physiological conditions, nearly all major components of the RAS including AGT, prorenin, renin, ANG I, and ANG II would be filtered by the glomerulus and taken up by the proximal tubules. In ANG II-dependent hypertension, the expression of AGT, prorenin, and (pro)renin receptors, and angiotensin-converting enzyme (ACE) is upregulated rather than downregulated in the kidney. Furthermore, hypertension damages the glomerular filtration barrier, which augments the filtration of circulating AGT, prorenin, renin, ANG I, and ANG II and their uptake in the proximal tubules. Together, increased local ANG II formation and augmented uptake of circulating ANG II in the proximal tubules, via activation of AT1 (AT1a) receptors and Na+/H+ ex-changer 3, may provide a powerful feedforward mechanism for promoting Na+ retention and the development of ANG II-induced hypertension.
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影响因子：
5.8
作者：
Chappell MC
通讯作者：
Chappell MC
影响因子：
8.3
作者：
Carey, RM
通讯作者：
Carey, RM
影响因子：
15.9
作者：
CHEN, M;HARRIS, MP;SCHNERMANN, J
通讯作者：
SCHNERMANN, J
影响因子：
--
作者：
Albiston, Anthony L.;Yeatman, Holly R.;Chai, Siew Yeen
通讯作者：
Chai, Siew Yeen
影响因子：
--
作者：
BRAAM, B;MITCHELL, KD;NAVAR, LG
通讯作者：
NAVAR, LG