Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats
Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats
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DOI：
10.1152/ajprenal.00058.2008
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发表时间：
2008-11-01
影响因子：
4.2
通讯作者：
Hishida, Akira
中科院分区：
文献类型：
--
作者：
Ohashi, Naro;Yamamoto, Tatsuo;Hishida, Akira
Ohashi N，Yamamoto T，Huang Y，Misaki T，Shiasawa H，Suzuki H，Togawa A，Suzuki S，Fujigaki Y，Nakagawa T，中村Y，Suzuki F，Kitagawa M，Hishida A.抗胸腺细胞血清肾炎大鼠肾内RAS活性和尿血管紧张素原排泄美国肾脏生理学杂志295：F1512-F1518，2008年。首次发表于2008年9月10日; doi：10.1152/ajprenal.00058.2008。循环和肾内肾素-血管紧张素系统（RAS）在肾小球肾炎中的不同作用尚未阐明。在这项研究中，我们调查了水平的循环和肾内RAS活性和尿血管紧张素原（AGT）排泄的抗胸腺细胞血清（ATS）肾炎诱导的ATS注射液（ATS组）。还检查了奥美沙坦（一种血管紧张素II（ANG II）1型受体阻滞剂（ARB））对肾炎发生的影响（ATS + ARB组）。此外，大鼠接受生理盐水注射而不是ATS（对照组）。与对照组相比，ATS组肾小球系膜增生伴短暂性蛋白尿（在第7天达到峰值）显著增加。与对照组相比，ATS组肾小球AGT mRNA、肾内ANG II和尿AGT排泄量在第7天显著增加。与ATS组相比，奥美沙坦给药（ATS + ARB组）显著降低了肾脏病变、蛋白尿和肾内RAS活性水平。此外，尿AGT排泄水平与肾小球损伤水平、尿蛋白排泄水平以及肾脏AGT和ANG II免疫反应水平相关。另一方面，与对照组相比，ATS组的血浆肾素活性显著降低，而ATS + ARB组的血浆肾素活性显著高于ATS组。这些数据表明，肾脏特异性RAS活性的增加，这与尿AGT排泄平行，在ATS肾炎的发展中起着重要作用。
Ohashi N, Yamamoto T, Huang Y, Misaki T, Fukasawa H, Suzuki H, Togawa A, Suzuki S, Fujigaki Y, Nakagawa T, Nakamura Y, Suzuki F, Kitagawa M, Hishida A. Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats. Am J Physiol Renal Physiol 295: F1512-F1518, 2008. First published September 10, 2008; doi:10.1152/ajprenal.00058.2008. The differential roles of circulating and intrarenal renin-angiotensin system (RAS) in glomerulonephritis have not been elucidated. In this study, we investigated the levels of circulating and intrarenal RAS activity and urinary angiotensinogen (AGT) excretion in anti-thymocyte serum (ATS) nephritis induced by an ATS injection (ATS group). The effect of olmesartan, an angiotensin II (ANG II) type 1 receptor blocker (ARB), on the development of nephritis was also examined (ATS + ARB group). In addition, the rats received a saline injection instead of ATS (control group). Mesangial proliferation with transient proteinuria, which peaked at day 7, was significantly increased in the ATS group compared with the control group. The levels of glomerular AGT mRNA, intrarenal ANG II, and urinary AGT excretion in the ATS group were increased significantly at day 7 compared with the control group. Administration of olmesartan (ATS + ARB group) significantly decreased the levels of renal lesions, proteinuria, and intrarenal RAS activity compared with the ATS group. In addition, the levels of urinary AGT excretion correlated with the levels of glomerular damage, urinary protein excretion, and immunoreactivity for AGT and ANG II in kidney. On the other hand, plasma renin activity was significantly lower in the ATS group compared with the control group and significantly higher in the ATS + ARB group than in the ATS group. These data suggest that an increase in kidney-specific RAS activity, which parallels urinary AGT excretion, plays an important role in the development of ATS nephritis.