Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice

作者：Dong Yi Fei; Liu Lei; Lai Zhong Fang; Yamamoto Eiichiro; Kataoka Keiichiro; Nakamura Taishi; Fukuda Masaya; Tokutomi Yoshiko; Nako Hisato; Ogawa Hisao; Kim Mitsuyama Shokei^*

来源：Journal of Hypertension, 2010, 28(7): 1554-1565.

DOI：10.1097/HJH.0b013e328338bb11

• angiotensin
• combination
• diabetic nephropathy
• oxidative stress
• renin

Objectives Addition of aliskiren, a direct renin inhibitor, to losartan provides additive reduction of urinary albumin excretion in type 2 diabetic patients. However, the detailed effect of aliskiren on type 2 diabetic nephropathy is still unknown. This study was undertaken to examine the efficacy of aliskiren and the combination of aliskiren with valsartan on type 2 diabetic nephropathy.
Methods db/db mice were treated with aliskiren (3 mg/kg per day), valsartan (5 or 10 mg/kg per day), combined aliskiren (3 mg/kg per day) and valsartan (5 mg/kg per day), and hydralazine (80 mg/kg per day), for 6 weeks, and the protective effects against diabetic nephropathy were compared among each group.
Results Aliskiren significantly attenuated albuminuria and glomerular mesangial matrix expansion in db/db mice, which was associated with the improvement of the increased glomerular transforming growth factor-beta and type IV collagen expressions, the increased macrophage infiltration, and the decreased glomerular nephrin expression of db/db mice. These protective effects of aliskiren in db/db mice were attributed to the attenuation of p(22phox)-related nicotinamide adenine dinucleotide phosphate oxidase-induced superoxide. Addition of aliskiren to valsartan treatment provided more beneficial effects on all the above-mentioned parameters than valsartan monotherapy.
Conclusion Aliskiren protected against type 2 diabetic nephropathy, through pleiotropic effects, and significantly enhanced the protective effects of valsartan against diabetic nephropathy in db/db mice.

• 出版日期2010-7