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

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.

• 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
• Journal: Journal of hypertension (J Hypertens) Vol. 28 Issue 7 Pg. 1554-65 (Jul 2010) ISSN: 1473-5598 [Electronic] England
• PMID: 20375908 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Collagen Type IV
• Fumarates
• Tetrazoles
• Transforming Growth Factor beta
• aliskiren
• Valsartan
• Valine
• Losartan

Topics

• 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)
• Valsartan