Intratubular renin-angiotensin system in hypertension.
Intratubular renin-angiotensin system in hypertension.
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DOI：
10.1161/hypertensionaha.110.163519
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Gonzalez-Villalobos RA
中科院分区：
文献类型：
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作者：
Navar LG;Kobori H;Prieto MC;Gonzalez-Villalobos RA
肾内肾素-血管紧张素（Ang）系统（RAS）的复杂性随着越来越多的证据表明其在肾间质和小管间室中具有强大的独立调节作用而不断显露出来。1-3早期报道表明，Ang II受体存在于近端小管刷状边缘，提示其生理作用。然而，由于灌木边缘的降解酶丰富，血管紧张素肽的浓度被认为相对较低。尽管如此，在近端和远端肾单元段的腔内Ang II受体的丰度维持了对Ang II的腔内作用的兴趣。5,6管状灌注研究表明，管腔Ang II改变管状钠和体积重吸收率1,5,7,8，支持了管腔Ang II受体的重要生理作用。当发现近端小管内Ang I和Ang II浓度远高于相应的血浆浓度时，范式转变发生了。7,10,11此外，当近端肾管液与过量肾素孵育时，Ang I的形成表明该段血管紧张素原（AGT）底物的利用率非常高。7,12此外，从灌注小管的下游段收集的管状液也具有与未灌注小管相似的Ang II浓度，从而支持局部来源。这些发现，以及近端小管细胞表达AGT mRNA和蛋白的证明13,14，为存在强大的生理上重要的小管RAS奠定了基础。
The complexity of the intrarenal renin-angiotensin (Ang) system (RAS) continues to reveal itself as evidence accumulates demonstrating its robust independent regulation in the interstitial and intratubular compartments within the kidney. 1–3 Early reports demonstrating the presence of Ang II receptors on the brush border of proximal tubules suggested physiological roles. 4 However, because of the abundance of degradating enzymes on the brush border, the concentrations of angiotensin peptides were considered to be relatively low. Nevertheless, the abundance of luminal Ang II receptors throughout proximal and distal nephron segments sustained interest in the luminal actions of Ang II. 5, 6 Tubular perfusion studies indicating that luminal Ang II alters tubular sodium and volume reabsorption rate1, 5, 7, 8 supported an important physiological role for luminal Ang II receptors. 9 A paradigm shift occurred when it was discovered that the proximal intratubular concentrations of Ang I and II were much greater than their corresponding plasma concentrations. 7, 10, 11 In addition, when proximal tubular fluid was incubated with excess renin, the resultant formation of Ang I indicated very high angiotensinogen (AGT) substrate availability in this segment. 7, 12 Furthermore, tubular fluid collected from downstream segments of perfused tubules also had Ang II concentrations similar to those in nonperfused tubules, thus supporting a local origin. 11 These findings, along with the demonstration that proximal tubule cells express AGT mRNA and protein, 13, 14 established the foundation for the existence of a robust physiologically important tubular RAS.