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Background/aims: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR)., Methods: Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-β-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated., Results: As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression., Conclusion: Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To investigate the effect of high glucose and losartan on cell proliferation and cyclooxygenase-2 (COX2) expression in normal human mesangial cells (NHMCs), and to examine the effect of losartan on COX2 and transforming growth factor-beta1 (TGF-beta1) expression in a model of diabetic nephropathy (DN)., Methods: NHMCs were cultured in vitro in high glucose media with or without losartan. NHMCs proliferation and COX2 expression were determined by WST-1, Western blot, and RT-PCR. The rat model of DN was produced by injections of streptozocin (STZ). After the treatment with losartan for 4 weeks, glomerular hypertrophy, urinary thromboxane B2 (TXB2) and 24 h urinary protein counts were measured, and COX2 and TGF-beta1 expressions were investigated using immunohistochemical techniques and RT-PCR., Results: Losartan dose-dependently inhibited the proliferation of NHMCs in response to high glucose. Losartan also decreased COX2 expression in NHMCs at high or low glucose concentrations. In vivo experiments found kidney weight/body weight (KW/BW), urinary TXB2 and 24 h urinary protein counts increased significantly in the DN group. Losartan reduced KW/BW, urinary TXB2, and 24 h urinary protein counts and significantly suppressed the over-expression of COX2 and TGF-beta1., Conclusion: Losartan reduces COX2 expression in NHMCs,especially at high glucose concentrations. Losartan could suppress the expression of COX2 and TGF-beta1 in the kidney of DN rats and attenuate the renal lesions caused by DN.