Submitted on February 3, 2008
Accepted on August 26, 2008
Intrarenal RAS activity and urinary angiotensinogen excretion in anti-thymocyte serum nephritis rats
Naro Ohashi1*, Tatsuo Yamamoto2, Yanjie Huang1, Taro Misaki1, Hirotaka Fukasawa1, Hiroyuki Suzuki1, Akashi Togawa1, Sayuri Suzuki3, Yoshihide Fujigaki1, Tsutomu Nakagawa4, Yukio Nakamura4, Fumiaki Suzuki4, Masatoshi Kitagawa5, and Akira Hishida1
1 First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
2 First Department of Medicine , Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; Faculty of Health Promotional Sciences, Hamamatsu University, Hamamatsu, Shizuoka, Japan
3 First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; Department of Biochemistry 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
4 Faculty of Applied Biological Science, Gifu University, Gifu, Gifu, Japan
5 Department of Biochemistry 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
* To whom correspondence should be addressed. E-mail: nohashi{at}tulane.edu.
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 (AngII) type 1 receptor blocker (ARB), on the development of nephritis was also examined (ATS+ARB group). In addition, the rats received 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 to the control group. The levels of glomerular AGT mRNA, intrarenal AngII and urinary AGT excretion in the ATS group were increased significantly at day 7 compared to the control group. Administration of olmesartan (ATS+ARB group) significantly decreased the levels of renal lesions, proteinuria and intrarenal RAS activity compared to 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 AngII in kidney. On the other hand, plasma renin activity was significantly lower in the ATS group compared to 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.
