Proximal tubule angiotensinogen modulation of arterial pressure.
Proximal tubule angiotensinogen modulation of arterial pressure.
复制标题
DOI：
10.1097/mnh.0b013e328359dbed
复制
发表时间：
2013-01
影响因子：
3.2
通讯作者：
Kohan DE
中科院分区：
文献类型：
--
作者：
Ramkumar N;Kohan DE
虽然现在已经很好地确定了完整的肾内肾素-血管紧张素系统的存在，但其在调节小管钠转运和血压中的作用还不完全清楚。最近的几项研究揭示了该系统的一个组成部分，近端小管衍生的血管紧张素原（AGT）。本文就AGT在近曲小管中的合成、调节及其功能作一综述。在正常钠摄入量下，近端小管S1和S2段内的AGT可能来自体循环，而S3段合成AGT。尿AGT可能主要反映近端小管来源的AGT。近端小管AGT的合成受高Na摄入、血管紧张素II和炎性细胞因子的调节。小鼠AGT在近曲小管中的转基因表达导致高血压。大鼠AGT在近端小管中的过表达导致高血压、通过NADPH氧化酶增强的活性氧产生、肾小管凋亡和肾小管间质纤维化;这些作用可以通过过氧化氢酶过表达来减轻。近端小管衍生的AGT具有调节血压和钠平衡的潜力，并促进肾损伤。与系统性肾素-血管紧张素系统的相互作用可能会影响近端小管衍生的AGT在肾脏中的作用。
Although the existence of a complete intrarenal renin–angiotensin system is now well established, its role in modulating tubule sodium transport and blood pressure is incompletely understood. Several recent studies have shed light on one component of the system, proximal tubule-derived angiotensinogen (AGT). This review discusses the synthesis, regulation and function of AGT in the proximal tubule. Under normal sodium intake, AGT within the S1 and S2 segments of the proximal tubule may derive from the systemic circulation, whereas the S3 segment synthesizes AGT. Urinary AGT likely primarily reflects proximal tubule-derived AGT. Proximal tubule AGT synthesis is regulated by high Na intake, angiotensin-II and inflammatory cytokines. Transgenic expression of mouse AGT in the proximal tubule causes hypertension. Overexpression of rat AGT in the proximal tubule leads to hypertension, enhanced reactive oxygen species generation via NADPH oxidase, tubular apoptosis and tubulointerstitial fibrosis; these effects can be mitigated by catalase overexpression. Proximal tubule-derived AGT has the potential to modulate blood pressure and sodium balance, and promote renal injury. Interactions with the systemic renin–angiotensin system may influence the role of proximal tubule-derived AGT in the kidney.