Feasibility of fluorescence energy transfer system for imaging the renoprotective
effects of aliskiren in diabetic mice
#MMPMID27216079
Kidokoro K
; Satoh M
; Itano S
; Kuwabara A
; Sasaki T
; Kashihara N
J Renin Angiotensin Aldosterone Syst
2016[Apr]; 17
(2
): 1470320315625704
PMID27216079
show ga
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.
free
free
free
