title: Rosuvastatin suppresses the oxidative response in the venous limb of an arteriovenous fistula and enhances the fistula blood flow in diabetic rats.
abstract: OBJECTIVE
  The blood flow in the arteriovenous (AV) fistula is significantly reduced in diabetic patients. Statins are known to mediate pleiotropic effects in the vascular endothelium and attenuate inflammatory responses. This study tested the vascular protective effect of rosuvastatin in an experimental model of AV fistula.
  
  
  METHODS
  One week after the induction of diabetes mellitus (DM) in rats, a fistula was created in the abdominal aorta and inferior vena cava. Rats received placebo or rosuvastatin (15 mg/kg/day) in chow for 2 weeks. The blood flow in the venous segments of the fistula was measured. The expression of proinflammatory genes and the generation of superoxide in the venous fistula were examined.
  
  
  RESULTS
  The blood flow and luminal diameter of the AV fistula was significantly enhanced in animals treated with rosuvastatin. Rosuvastatin attenuated the expression of inducible nitric oxide synthase, NADPH oxidase, and monocyte chemotactic protein-1 in the fistula. The levels of superoxide anions and proinflammatory cytokines were also suppressed in rosuvastatin-treated animals. Neointimal formation in the AV fistula was not affected following treatment with rosuvastatin.
  
  
  CONCLUSIONS
  We demonstrated that rosuvastatin improves luminal dilatation and blood flow in the AV fistula of subjects with DM. These vascular protective effects of rosuvastatin are most likely mediated by the attenuation of proinflammatory activities in the remodeled vasculature.
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Fang
authors.forename: Jun-Neng
authors.initials: JN
authors.lastname: Roan
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Hsu
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Chang
authors.forename: Chein-Chi
authors.initials: CC
authors.lastname: Huang
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Tsai
authors.forename: Chen-Fuh
authors.initials: CF
authors.lastname: Lam
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000503:physiopathology / Q000601:surgery; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D001783:Blood Flow Velocity; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D005464:Fluorobenzenes / Q000494:pharmacology*; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D058426:Neointima; D018384:Oxidative Stress / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood; D013997:Time Factors; D014682:Vena Cava, Inferior / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D011743:Pyrimidines; D013449:Sulfonamides; D013481:Superoxides; D000068718:Rosuvastatin Calcium