Angiotensin Ⅱ stimulates the expression of NADPH oxidase subunit p47phox mRNA in kidney in a rat model of hyperoxaluria / 中国病理生理杂志

ABSTRACT

AIM: To investigate the roles of angiotensin Ⅱ and NADPH oxidase in the development of renal oxidative stress (OS) in a rat model of hyperoxaluria. METHODS:Animal model of hyperoxaluria was established in a-dult male Sprague - Dawley rats by administration of 0.8% ethylene glycol (EC) in drinking water for 4 weeks. Simultaneous treatment with apocynin (0.2g·kg~(-1)·d~(-1))or losartan (30 mg·kg~(-1)·d~(-1) ) by intragastric administration were performed in rats, respectively. At the end of the study, markers for the state of oxidative stress (OS) , urinary 8 - IP and the enzymatic activity of superoxide dismutase ( SOD) in kidney homogenates were assessed. The concentration of angiotensin H in kidney homogenates was determined using radioimmunoassay method. Expression of NADPH oxidase subunit p47phox in kidney was localized and evaluated by immunohistochemistry and real time - PCR, respectively. RESULTS: p47phox expressed widely in the kidneys of this rat model, including renal cortex, inner medulla and outer medulla. Compared with the control, OS developed significantly in rats received EG, with increased expression of p47phox mRNA in kidneys. Renal angiotensin Ⅱ also increased significantly. Treatment with apocynin or losartan significantly reduced the excretion of urinary 8 - IP, restored the SOD activity, with decrease in the expression of p47phox mRNA in kidney, but the levels of those OS markers in apocynin or losartan treated rats were still higher than those in normal controls. CONCLUSION: Results suggest that renal Ang Ⅱ and its stimulation of NADPH oxidase may partially account for the development of OS in kidney in this rat model of hyperoxaluria.