The Role of Renin-Angiotensin System in Experimental Unilateral Ureteral Obstruction / 대한신장학회잡지

ABSTRACT

In order to evaluate the renal expression of renin, TGF-beta, TNF-alpha, IL-6, MCP-1, endothelin-1, osteopontin, and the role of renin-angiotensin system(RAS) in renal injury mechanism of experimental unilateral ureteral obstruction(UUO), 44 male Sprague-Dawley rats weighing 260-280g underwent sham operation(n= 8), UUO without treatment(n=12), UUO with angiotensin converting enzyme inhibitor(ACEI, enalapril 100 mg/kg body weight in drinking water, n=12) and UUO with angiotensin II AT1 receptor antagonist(AT1 RA, losartan 300mg/Kg body weight in drinking water, n= 12) under thiopental sodium anesthesia(50mg/kg, body weight, I.P.). Half number of each group was sacrificed at 3 and 7 days after surgery. With standard point count method, we evaluated the magnitude of tubulointerstitial mononuclear cell infiltration and relative volume of interstitium by light microscopic examination (PAS stain and immunohistochemistry for ED-1). Competitive RT-PCR was performed for the estimation of renin, TGF-beta, TNF-alpha, IL-6, MCP-1, endothelin-1, osteopontin and beta-actin gene expression levels of the kidneys. Renal gene expressions of renin, TGF-beta, MCP-1, TNF-alpha, IL-6, endothelin-1, and osteopontin of untreated control UUO rats were significantly increased compared to sham operated rats at 3 and 7 days after surgery. The level of TGF-beta, TNF-alpha, IL-6 and endothelin-1 gene expressions of ACEI treated UUO rats was significantly lower than those of untreated control UUO rats. AT1 RA treated UUO rats also showed significantly lower level of TGF-beta and osteopontin gene expression than those of control UUO group. Untreated control UUO rats showed significantly increased mononuclear cell infiltration of tubulointerstitium and relative volume of interstitium of the kidney compared to sham operated rats. ACEI or AT1 RA treated UUO rats showed significantly less relative volume of interstitium and mononuclear cell infiltration than those of untreated UUO rats(p<0.05, p<0.05). With the above result, we speculate that the upregulation of renin, TGF-beta, MCP-1, TNF-alpha, IL-6, osteopontin and endothelin-1 genes is closely related to the progressive renal injury process in this model and at least in part, the early activation of renin angiotensin system of the kidney is involved in this mechanism.