title: Treatment with high dose of atorvastatin reduces vascular injury in diabetic rats.
abstract: Previous reports showed conflicting results regarding the treatment effects of statin on Diabetes mellitus (DM). We investigated how treatment with high dose of atorvastatin affects the impaired vascular function in diabetic rats.
  
  
  
  Atorvastatin (80mg/kg/day, oral gavage, 4 weeks) or its vehicle was administered to male control or streptozotocin (STZ)-induced diabetic rats. Aortic segments were used to investigate the vascular reactivity, protein expression of cyclooxygenase-2 (COX-2) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) 1 (NOX1) and superoxide anions levels.
  
  
  
  Atorvastatin treatment did not affect glycemia levels. In diabetic rats, the vascular reactivity to phenylephrine increased compared with controls and the atorvastatin treatment reduced this response. Removal of the endothelium increased the response to phenylephrine in control rats, but not in the diabetic group. Atorvastatin increased the endothelial modulation in diabetic rats. L-NAME (100μM) increased the reactivity in all groups, but this effect was greater in atorvastatin-treated diabetic rats. Indomethacin (10μM) and NS398 (1μM) decreased the contractile response in diabetic rats and atorvastatin reversed these effects, without changing COX-2 expression. Apocynin (30μM) decreased the phenylephrine response in diabetic rats, which also showed increased NOX1 and superoxide anions; these effects were prevented by atorvastatin treatment.
  
  
  
  The results suggest that treatment with high dose of atorvastatin, independent of glycemia, improves endothelial function in aortas from diabetic rats by reducing the constrictor prostanoids derived from COX-2 and by reducing the oxidative stress by NADPH oxidase, as well as a possible increasing of nitric oxide participation.
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil. Electronic address: fabianavsimoes@hotmail.com.
authors.forename: Fabiana Vieira
authors.initials: FV
authors.lastname: Simões
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil. Electronic address: pri.ftp@gmail.com.
authors.forename: Priscila Rossi
authors.initials: PR
authors.lastname: de Batista
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil. Electronic address: tatianibotelho@hotmail.com.
authors.forename: Tatiani
authors.initials: T
authors.lastname: Botelho
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil. Electronic address: rogeriofaustinoribeiro@hotmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Hertel Ribeiro
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil. Electronic address: ale_padilha@hotmail.com.
authors.forename: Alessandra Simão
authors.initials: AS
authors.lastname: Padilha
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brazil; Escola Superior de Ciências da Santa Casa de Misericórdia de Vitória (EMESCAM), Vitória, ES, Brazil. Electronic address: daltonv2@terra.com.br.
authors.forename: Dalton Valentim
authors.initials: DV
authors.lastname: Vassallo
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D000069059:Atorvastatin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; D014665:Vasodilator Agents; D013481:Superoxides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010656:Phenylephrine; D013311:Streptozocin; D000069059:Atorvastatin; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: Atorvastatin; Cyclooxygenase-2; Diabetes mellitus; Oxidative stress; Vascular function