title: Feasibility of fluorescence energy transfer system for imaging the renoprotective effects of aliskiren in diabetic mice.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Fluorescence resonance energy transfer could provide a new tool for evaluating tissue and plasma enzymatic activity.
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kidokoro
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan msatoh@med.kawasaki-m.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Itano
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kuwabara
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Nephrology and Hypertension, Kawasaki Medical School, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kashihara
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005240:Feasibility Studies; D031541:Fluorescence Resonance Energy Transfer; D005650:Fumarates / Q000494:pharmacology* / Q000627:therapeutic use; D021621:Imaging, Three-Dimensional; D007668:Kidney / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects; D046911:Macromolecular Substances / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis; D010539:Permeability / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D012083:Renin / Q000097:blood; D013481:Superoxides / Q000378:metabolism
chemical_list: D000577:Amides; D005650:Fumarates; D046911:Macromolecular Substances; D020011:Protective Agents; D013481:Superoxides; D009569:Nitric Oxide; C446481:aliskiren; D012083:Renin
keywords: Renin; albuminuria; diabetic nephropathy; fluorescence resonance energy transfer; in vivo imaging