Anderson S

Atsunori Kuwabara

Burns KD

Cousin C

Durvasula RV

Furukawa M

Gandhi S

Hollenberg NK

Kang JJ

Kengo Kidokoro

Lai KN

Lange S

Minoru Satoh

Naoki Kashihara

Nguyen G

Palmer SC

Peti-Peterdi J

Satoh M

Seiji Itano

Singh R

Tamaki Sasaki

Velez JC

Vidotti DB

Wang W

Yoo TH

Introduction: We investigated the feasibility of using a fluorescence resonance energy transfer system to image enzymatic activity in order to evaluate the effects of aliskiren (a direct renin inhibitor) on diabetic nephropathy. Materials and methods: First, we induced diabetes in C57BL/6J mice using streptozotocin, then treated them with either aliskiren (25 mg/kg/day) or the angiotensin type 1 receptor blocker valsartan (15 mg/kg/day) for four weeks. Finally, we utilized renin fluorescence resonance energy transfer substrate to assess renin activity. Results: Renin activity was much higher in the kidneys of diabetic mice compared to those of the non-diabetic control mice. While aliskiren inhibited this activity, valsartan did not. We noted that production of reactive oxygen species intensified and the bioavailability of nitric oxide diminished in the glomeruli of diabetic mice. Aliskiren and valsartan significantly ameliorated these effects. They suppressed glomerular production of reactive oxygen species and urinary albumin excretion. In fact, urinary albumin excretion in diabetic mice treated with aliskiren or valsartan was lower than that in untreated diabetic mice. Furthermore, aliskiren and valsartan significantly reduced glomerular permeability by maintaining the glomerular endothelial surface layer. Conclusion: Fluorescence resonance energy transfer could provide a new tool for evaluating tissue and plasma enzymatic activity. </jats:sec

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Journal of the Renin-Angiotensin-Aldosterone System

Feasibility of fluorescence energy transfer system for imaging the renoprotective effects of aliskiren in diabetic mice

Feasibility of fluorescence energy transfer system for imaging the renoprotective effects of aliskiren in diabetic mice

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