Early stage of obesity potentiates nitric oxide reduction during the development of renal failure.
BACKGROUND
Obesity is a serious health problem associated with the pathogenesis of various metabolic diseases. Nitric Oxide (NO) plays an important role in kidney function and altered NO levels have been associated with the pathogenesis of obesity. Therefore, we aimed to study whether an early stage of obesity contributes with progression of renal failure through further NO impairment.


METHODS
Male C57BL/6 mice were fed with a high-fat diet (HFD) or a normal diet (ND) during 2 weeks. All mice underwent either sham surgery (sham) or 5/6 nephrectomy (Np). One group of HFD Np mice was treated with antioxidants plus L-arginine. Kidney damage parameters were assessed and eNOS metabolism was evaluated.


RESULTS
Mice on a HFD increased body weight, eNOS protein and mRNA expression, and radical oxygen species (ROS). Urine nitrites excretion, urine volume, and plasma BH4 were decreased. In HFD mice, 5/6 Np further increased BH2 and urine protein concentration, ROS levels, and eNOS mRNA expression. The decrease in BH4 plasma levels and urine nitrites excretion was accentuated. NO synthesis stimulation with the antioxidants + L-arginine treatment prevented all these changes.


CONCLUSIONS
The early changes in NO metabolism are associated with an early stage of obesity. This effect on NO potentiates kidney damage development.
CINVESTAV Monterrey, Apodaca, Nuevo León, Mexico.
Ana María
AM
Gámez-Méndez
Hilda
H
Vargas-Robles
Mónica
M
Arellano-Mendoza
Erika
E
Cruz-Laguna
Amelia
A
Rios
Bruno
B
Escalante
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D009569:Nitric Oxide / Q000378:metabolism* / Q000652:urine; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D012307:Risk Factors; D015430:Weight Gain
D000975:Antioxidants; D015415:Biomarkers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D001708:Biopterins; D009569:Nitric Oxide; C017226:7,8-dihydrobiopterin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C003402:sapropterin