Reduction of albuminuria by angiotensin receptor blocker beyond blood pressure lowering: Evaluation in megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic diabetic nephropathy mouse model

Shuichi Ohtomo, Masaki Ito, Yuko Izuhara, Charles Van Ypersele De Strihou, Toshio Miyata

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aim: Antihypertensive agents inhibiting the renin-angiotensin system (RAS), such as angiotensin II type 1 receptor blockers (ARB), are now part of the standard treatment of patients with diabetic nephropathy, regardless of the presence of systemic hypertension. Whether ARB achieve better renoprotection than other RAS-independent antihypertensive drugs has been an issue of controversy. Several lines of large clinical studies provided better renoprotection of ARB. However, a recent meta-analysis argued against additional benefits of ARB beyond blood pressure. We generated a novel mouse model of diabetic nephropathy; that is, megsin/receptor for advanced glycation end products/inducible nitric oxide synthase triple transgenic mice. This model is normotensive but progressively develops severe diabetic nephropathy that resembles those observed in humans. Methods: In the present study, we tested whether olmesartan (ARB) achieves better renoprotection than amlodipine (calcium channel blocker). Drug treatment was initiated at the age of 6 weeks and lasted for 12 weeks. Results: This model develops significant glomerular lesions and albuminuria even at the age of 5 weeks. Despite equal blood pressure lowering, only olmesartan suppressed the progression of albuminuria. Neither olmesartan nor amlodipine modified histological lesions. Conclusion: Proteinuria and its reduction are known to predict the progression of diabetic nephropathy. Our results support the additional benefit of ARB beyond blood pressure lowering.

Original languageEnglish
Pages (from-to)517-521
Number of pages5
JournalNephrology
Volume13
Issue number6
DOIs
Publication statusPublished - 2008 Sep 1
Externally publishedYes

Keywords

  • Albuminuria
  • Angiotensin receptor blocker
  • Animal model
  • Calcium channel blocker
  • Diabetic nephropathy

ASJC Scopus subject areas

  • Nephrology

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