| Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice. | |
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MedLine Citation:
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PMID: 20375908 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 28 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-24 Completed Date: 2010-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 1554-65 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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J Hypertens. 2010 Jul;28(7):1382-3
[PMID:
20574248
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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