Document Detail


Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice.
MedLine Citation:
PMID:  20375908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 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.
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.
Authors:
Yi-Fei Dong; Lei Liu; Zhong-Fang Lai; Eiichiro Yamamoto; Keiichiro Kataoka; Taishi Nakamura; Masaya Fukuda; Yoshiko Tokutomi; Hisato Nako; Hisao Ogawa; Shokei Kim-Mitsuyama
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-24     Completed Date:  2010-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1554-65     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Albuminuria / complications,  metabolism
Amides / pharmacology*
Animals
Collagen Type IV / pharmacology
Diabetes Mellitus, Type 2 / complications*,  drug therapy
Diabetic Nephropathies / drug therapy,  metabolism*,  prevention & control*
Drug Synergism
Fumarates / pharmacology*
Kidney Glomerulus / metabolism
Losartan / pharmacology
Male
Mice
Mice, Inbred C57BL
Tetrazoles / pharmacology*
Transforming Growth Factor beta / metabolism,  pharmacology
Valine / analogs & derivatives*,  pharmacology
Chemical
Reg. No./Substance:
0/Amides; 0/Collagen Type IV; 0/Fumarates; 0/Tetrazoles; 0/Transforming Growth Factor beta; 0/aliskiren; 114798-26-4/Losartan; 137862-53-4/valsartan; 7004-03-7/Valine
Comments/Corrections
Comment In:
J Hypertens. 2010 Jul;28(7):1382-3   [PMID:  20574248 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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