Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice - PubMed
Comparative Study
. 2010 Jul;28(7):1554-65.
doi: 10.1097/HJH.0b013e328338bb11.
Affiliations
- PMID: 20375908
- DOI: 10.1097/HJH.0b013e328338bb11
Comparative Study
Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice
Yi-Fei Dong et al. J Hypertens. 2010 Jul.
Abstract
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.
Comment in
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More complete renin-angiotensin system blockade: better outcomes or smoke and mirrors.
Bakris GL, Bidani A. Bakris GL, et al. J Hypertens. 2010 Jul;28(7):1382-3. doi: 10.1097/HJH.0b013e328339f971. J Hypertens. 2010. PMID: 20574248 No abstract available.
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