Regulation of intrarenal angiotensin II in hypertension
Regulation of intrarenal angiotensin II in hypertension
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DOI：
10.1161/hy0202.103821
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发表时间：
2002-02-01
期刊：
影响因子：
8.3
通讯作者：
Kobori, H
中科院分区：
文献类型：
--
作者：
Navar, LG;Harrison-Bernard, LM;Kobori, H
肾内血管紧张素II（Ang II）是由几个复杂的过程，涉及从系统交付和肾内形成的底物，以及受体介导的内化形成。肾内血管紧张素II存在显著的区室化，肾间质液和近端小管液中的水平远高于循环水平。在血管紧张素II依赖性高血压中，即使肾内肾素表达和含量受到抑制，肾内血管紧张素II水平也会升高。对输注Ang II的大鼠的研究表明，肾内Ang II的增加部分归因于通过Ang II I型（AT（1））受体机制吸收循环Ang II，也归因于Ang II的持续内源性产生。一些内化的Ang II在轻和重内涵体中积累，因此可能用于细胞内作用。肾内血管紧张素Ⅱ水平的升高还可产生正反馈作用，使肾内血管紧张素原（angiotensinogen，AGT）mRNA和蛋白水平升高，从而进一步促进高血压肾内血管紧张素Ⅱ水平的升高。此外，肾脏AT（1）受体蛋白和mRNA水平得以维持，从而使Ang II水平升高，引发进行性效应。肾内血管紧张素Ⅱ活性和AGT产生的增加与尿AGT排泄率的增加有关。尿AGT排泄率与肾脏Ang Ⅱ含量呈明显相关性，提示尿AGT可作为Ang Ⅱ依赖性高血压的一个指标。总的来说，这些数据支持肾内血管紧张素II在高血压发病机制中的重要作用。
Intrarenal angiotensin II (Ang II) is regulated by several complex processes involving formation from both systemically delivered and intrarenally formed substrate, as well as receptor-mediated internalization. There is substantial compartmentalization of intrarenal Ang II, with levels in the renal interstitial fluid and in proximal tubule fluid being much greater than can be explained from the circulating levels. In Ang II-dependent hypertension, elevated intrarenal Ang II levels occur even when intrarenal renin expression and content are suppressed. Studies in Ang II-infused rats have demonstrated that augmentation of intrarenal Ang II is due, in part, to uptake of circulating Ang II via an Ang II type I (AT(1)) receptor mechanism and also to sustained endogenous production of Ang II. Some of the internalized Ang II accumulates in the light and heavy endosomes and is therefore potentially available for intracellular actions. The enhanced intrarenal Ang II also exerts a positive feedback action to augment intrarenal levels of angiotensinogen (AGT) mRNA and protein, which contribute further to the increased intrarenal Ang II in hypertensive states. In addition, renal AT(1) receptor protein and mRNA levels are maintained, allowing increased Ang II levels to elicit progressive effects. The increased intrarenal Ang II activity and AGT production are associated with increased urinary AGT excretion rates. The urinary AGT excretion rates show a clear relationship to kidney Ang II content, suggesting that urinary AGT may serve as an index of Ang II-dependent hypertension. Collectively, the data support a powerful role for intrarenal Ang II in the pathogenesis of hypertension.