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

Ohtomo, Shuichi;Ito, Masaki;Izuhara, Yuko;Van Ypersele de Strihou, Charles;Miyata, Toshio
(2008) Nephrology — Vol. 13, n° 6, p. 517-521 (2008)

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Authors
  • Ohtomo, Shuichi
    Author
  • Ito, Masaki
    Author
  • Izuhara, Yuko
    Author
  • Van Ypersele de Strihou, CharlesUCLouvain
    Author
  • Miyata, Toshio
    Author
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.
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Ohtomo, S., Ito, M., Izuhara, Y., Van Ypersele de Strihou, C., & Miyata, T. (2008). 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. Nephrology, 13(6), 517-521. https://doi.org/10.1111/j.1440-1797.2008.00929.x (Original work published 2008)