Expression Of Angiotensin â…¡ And Its Receptors In Chronic Cyclosporine Nephrotoxicity

Objective:To investigate the expression of angiotensinⅡ(AngⅡ) and its receptors in a rat model of chronic cyclosporine nephrotoxicity.Method:Chronic CsA nephrotoxicity was induced in Sprague-Dawley rats by administering CsA (15 mg/kg s.c.) for 4 weeks. Body weight, systolic blood pressure, and renal function were monitored. In addition, renal histopathology (tubulointerstitial fibrosis) and expressions of AngⅡand its receptors (AT1 and AT2) were examined.Results:Compared with the control rats, CsA-treated rats showed loss of body weight and renal dysfunction, with the development of striped tubulointerstitial fibrosis. Immunohistochemistry revealed that immunoreactivity of AngⅡsignificantly increased in the CsA-treated rat kidney (47±4 vs.13±4, P< 0.01) in parallel with tubulointerstitial fobrisis (r= 0.769, P< 0.001), which mainly localized to the juxtaglomerular afferent arterioles. This increase followed by decreased AT1 expression [(114±14)%vs. (42±6)%, P< 0.01] and increased AT2 expression [(129±23)%vs. (469±43)%, P< 0.01].Conclusions:These findings suggest that intrarenal renin-angiotensin system is activated by upregulating AngⅡimmunoreactivity in a rat model of chronic CsA nephrotoxicity, and this upregulation may be correlated to the tubulointerstitial fibrosis.