title: Nox1 overexpression potentiates angiotensin II-induced hypertension and vascular smooth muscle hypertrophy in transgenic mice.
abstract: BACKGROUND
  Reactive oxygen species (ROS) have been implicated in the development of cardiovascular pathologies. NAD(P)H oxidases (Noxes) are major sources of reactive oxygen species in the vessel wall, but the importance of individual Nox homologues in specific layers of the vascular wall is unclear. Nox1 upregulation has been implicated in cardiovascular pathologies such as hypertension and restenosis.
  
  
  RESULTS
  To investigate the pathological role of Nox1 upregulation in vascular smooth muscle, transgenic mice overexpressing Nox1 in smooth muscle cells (TgSMCnox1) were created, and the impact of Nox1 upregulation on the medial hypertrophic response during angiotensin II (Ang II)-induced hypertension was studied. These mice have increased expression of Nox1 protein in the vasculature, which is accompanied by increased superoxide production. Infusion of Ang II (0.7 mg/kg per day) into these mice for 2 weeks led to a potentiation of superoxide production compared with similarly treated negative littermate controls. Systolic blood pressure and aortic hypertrophy were also markedly greater in TgSMCnox1 mice than in their littermate controls. To confirm that this potentiation of vascular hypertrophy and hypertension was due to increased ROS formation, additional groups of mice were coinfused with the antioxidant Tempol. Tempol decreased the level of Ang II-induced aortic superoxide production and partially reversed the hypertrophic and hypertensive responses in these animals.
  
  
  CONCLUSIONS
  These data indicate that smooth muscle-specific Nox1 overexpression augments the oxidative, pressor, and hypertrophic responses to Ang II, supporting the concept that medial Nox1 participates in the development of cardiovascular pathologies.
authors.affiliation: Division of Cardiology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Dikalova
authors.forename: Roza
authors.initials: R
authors.lastname: Clempus
authors.forename: Bernard
authors.initials: B
authors.lastname: Lassègue
authors.forename: Guangjie
authors.initials: G
authors.lastname: Cheng
authors.forename: James
authors.initials: J
authors.lastname: McCoy
authors.forename: Sergey
authors.initials: S
authors.lastname: Dikalov
authors.forename: Alejandra
authors.initials: A
authors.lastname: San Martin
authors.forename: Alicia
authors.initials: A
authors.lastname: Lyle
authors.forename: David S
authors.initials: DS
authors.lastname: Weber
authors.forename: Daiana
authors.initials: D
authors.lastname: Weiss
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.forename: Harald H H W
authors.initials: HH
authors.lastname: Schmidt
authors.forename: Gary K
authors.initials: GK
authors.lastname: Owens
authors.forename: J David
authors.initials: JD
authors.lastname: Lambeth
authors.forename: Kathy K
authors.initials: KK
authors.lastname: Griendling
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D006984:Hypertrophy; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics*
chemical_list: D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human