title: Effects of nitric oxide on renal interstitial fibrosis in rats with unilateral ureteral obstruction.
abstract: OBJECTIVE
  It is well recognized that microvascular injury is a major determinant of renal fibrosis. Mounting evidence shows that nitric oxide (NO) plays an important role in angiogenesis. Therefore, we investigated to the effects of NO on kidney angiogenesis and renal fibrosis.
  
  
  METHODS
  In the present study, a unilateral ureteral obstruction (UUO) model was established with L-arginine (L-Arg, 1 g/dl) and N-nitro-L-arginine methyl ester (L-NAME, 5 mg/dl) serving as interference factors. We investigated the alteration of NO concentration with spectrophotometry, peritubular capillary (PTC) density with aminopeptidase P (JG12) immunohistochemical staining, and the expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) with immunohistochemical staining and Western blotting at weeks 2, 3 and 4.
  
  
  RESULTS
  Our findings showed that the expressions of VEGF, eNOS and PTC density were significantly decreased in rats with UUO, which was accompanied by a progressive increase in HIF-1α, TGF-β1 and an area of renal interstitial fibrosis. The administration of L-Arg promoted the synthesis of NO and significantly elevated the expressions of VEGF, eNOS and PTC density with the conspicuous loss of HIF-1α and TGF-β1 expressions and ultimately ameliorated renal fibrosis, which was markedly aggravated by L-NAME administration.
  
  
  CONCLUSIONS
  These findings demonstrate that NO appears to play an important role in kidney angiogenesis and in slowing the progression of renal interstitial fibrosis, which suggests that NO may serve as a novel therapeutic strategy for preventing renal fibrosis as well as fibrosis in other organs.
authors.affiliation: Department of Nephrology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, PR China. sdxyfy@yahoo.cn
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Yafen
authors.initials: Y
authors.lastname: Wang
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.forename: Aiguo
authors.initials: A
authors.lastname: Xiao
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester