Expression of angiotensin II and its receptors in a rat model of chronic cyclosporine nephrotoxicity
10.3724/SP.J.1008.2010.01286
- Author:
Ying-Shun JIN
1
Author Information
1. Nephrology and Dialysis Unit
- Publication Type:Journal Article
- Keywords:
Angiotensin II;
Angiotensin receptors;
Chronic cyclosporine nephrotoxicity;
Interstitial nephritis
- From:
Academic Journal of Second Military Medical University
2010;31(12):1286-1290
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the expression of angiotensin II ( Ang II) and its receptors in a rat model of chronic cyclosporine (CsA) nephrotoxicity. Methods: Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg s. c.) for 4 weeks. The body weight, systolic blood pressure, serum CsA, serum creatinine (Cr), and creatinine clearance rate (Ccr) of rats were examined in each group. Trichrome staining was used to observe the tubulointerstitial fibrosis; expressions of Ang II and its receptors (AT1 and AT2) were examined by immunohistochemical staining and Western blotting analysis. Results: Compared with the control rats, CsA-treated rats showed decreased body weight, increased Cr, decreased Ccr and tubulointerstitial fibrosis (P < 0.01). Immunohistochemistry revealed that the immunoreactivity of Ang II was significantly increased in the CsA-treated rats (47±7 vs 13±4, P < 0.01), with the immunoreactivity mainly locating to the juxtaglomerular afferent arterioles, and the immunoreactivity was significantly correlated with tubulointerstitial fibrosis (r=0. 769, P<0.001). Western blotting analysis showed significantly decreased AT1 expression ([114±14]% vs [42±6]%, P<0.01) and increased AT2 expression ([129±23]% vs [469±43]%, P<0.01). Conclusion: The findings of our study suggest that the intrarenal renin-angiotensin system is activated during chronic CsA nephrotoxicity, which is manifested by increased Ang II immunoreactivity, and this increased immunoreactivity is closely related to tubulointerstitial fibrosis.
