title: Dietary arginine supplementation attenuates renal damage after relief of unilateral ureteral obstruction in rats.
abstract: BACKGROUND
  Progression of renal injury after relief of unilateral ureteral obstruction (UUO) has been demonstrated. Nitric oxide (NO) may be an effective intervention due to its vasodilatory, antifibrotic, and anti-apoptotic effects. Herein, we used dietary L-arginine (ARG) supplementation in a UUO relief model.
  
  
  METHODS
  This study comprised group 1, control (no treatment). All other rats were subject to 3-day UUO, which was then relieved, and the rats maintained for 7 additional days. Group 2, no additional treatment; group 3, L-ARG; group 4, L-NAME, NO synthase inhibitor; group 5, ARG and L-NAME. Urinary NO(2/3) was quantified. GFR and ERPF were measured at day 10. Interstitial fibrosis and fibroblast expression, macrophage infiltration, tubular apoptosis, and proliferation, NOS expression, and the levels of tissue TGF-beta were evaluated.
  
  
  RESULTS
  Urinary NO(2/3) was significantly increased by ARG treatment and decreased by L-NAME. GFR and ERPF measured 7 days following relief were not significantly different in the previously obstructed kidneys (POK) of groups 2 and 3. L-NAME significantly reduced GFR and ERPF in the POK. ARG significantly reduced apoptosis, macrophage infiltration, and fibroblast expression in the POK. L-NAME exacerbated the effects on apoptosis and fibroblasts. Fibrosis was minimal in groups 1 through 3, but was significantly increased by L-NAME. ARG did not affect renal NOS expression and tissue TGF-beta1 levels.
  
  
  CONCLUSIONS
  Dietary ARG supplementation during UUO relief did not improve ERPF or GFR. However, renal damage, including fibrosis, apoptosis, and macrophage infiltration was significantly improved by ARG treatment. This suggests that increasing NO availability could be beneficial in the setting of UUO relief.
authors: Institute for Pediatric Urology, Department of Urology, New York, New York 10021, USA.
authors: Keiichi
authors: K
authors: Ito
authors: Jie
authors: J
authors: Chen
authors: Surya V
authors: SV
authors: Seshan
authors: Jonathan J
authors: JJ
authors: Khodadadian
authors: Rachel
authors: R
authors: Gallagher
authors: Maher
authors: M
authors: El Chaar
authors: E Darracott
authors: ED
authors: Vaughan
authors: Dix P
authors: DP
authors: Poppas
authors: Diane
authors: D
authors: Felsen
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000652:urine; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000652:urine; D009929:Organ Size; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D018809:Proliferating Cell Nuclear Antigen; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester