Add-on aliskiren elicits stronger renoprotection than high-dose valsartan in type 2 diabetic KKAy mice that do not respond to low-dose valsartan.

Abstract

We hypothesized that aliskiren provides renoprotection in diabetic animals that did not receive sufficient renoprotection by AT1-receptor antagonist treatment. Type 2 diabetic KKAy mice were treated with group 1: vehicle or group 2: valsartan (15 mg/kg per day) from 12 to 16 weeks of age. The mice were subsequently divided into 4 groups and treated with the following combinations of drugs for another 6 weeks: 1: group 1 kept receiving vehicle, 2: group 2 continuously received 15 mg/kg per day of valsartan (Val-Val15), 3: group 2 received 50 mg/kg per day of valsartan (Val-Val50), 4: group 2 continuously received 15 mg/kg per day of valsartan with 25 mg/kg per day of aliskiren (Val-Val+Ali). Aliskiren exerted significant anti-albuminuric effects, whereas valsartan failed to ameliorate the albuminuria in the first four weeks. Surprisingly, the increasing dosage of valsartan in the Val-Val50 group showed non-significant tendencies to attenuate the albuminuria compared with vehicle infusion. Val-Val+Ali significantly suppressed the development of albuminuria and podocyte injury. Val-Val50 and Val-Val+Ali showed similar suppression of angiotensin II contents in the kidney of KKAy mice. In conclusion, the anti-albuminuric effect that was observed in the type 2 diabetic mice showing no anti-albuminuric effect by valsartan can be attributed to the add-on aliskiren.

• Authors: Bai Lei, Daisuke Nakano, Yu-Yan Fan, Kento Kitada, Hirofumi Hitomi, Hiroyuki Kobori, Hirohito Mori, Tsutomu Masaki, Akira Nishiyama
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 119 Issue 2 Pg. 131-8 ( 2012) ISSN: 1347-8648 [Electronic] Japan
• PMID: 22673148 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Angiotensin II Type 1 Receptor Blockers
• Blood Glucose
• Fumarates
• RNA, Messenger
• Tetrazoles
• Angiotensin II
• aliskiren
• Valsartan
• Renin
• Valine

Topics

• Albuminuria (drug therapy, metabolism)
• Amides (administration & dosage)
• Angiotensin II (metabolism)
• Angiotensin II Type 1 Receptor Blockers (administration & dosage)
• Animals
• Blood Glucose (analysis)
• Blood Pressure (drug effects)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, pathology)
• Drug Therapy, Combination
• Fumarates (administration & dosage)
• Kidney (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (metabolism)
• Renin (antagonists & inhibitors, genetics)
• Tetrazoles (administration & dosage)
• Valine (administration & dosage, analogs & derivatives)
• Valsartan