title: Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice.
abstract: OBJECTIVE
  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 p22(phox)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Zhong-Fang
authors.initials: ZF
authors.lastname: Lai
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kataoka
authors.forename: Taishi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masaya
authors.initials: M
authors.lastname: Fukuda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tokutomi
authors.forename: Hisato
authors.initials: H
authors.lastname: Nako
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000378:metabolism; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D024141:Collagen Type IV / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control*; D004357:Drug Synergism; D005650:Fumarates / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013777:Tetrazoles / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000577:Amides; D024141:Collagen Type IV; D005650:Fumarates; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; C446481:aliskiren; D000068756:Valsartan; D014633:Valine; D019808:Losartan