title: Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase.
abstract: OBJECTIVE
  Reactive oxygen species are believed to be an important determinant of vascular growth. We examined effects of genetic deficiency of copper-zinc superoxide dismutase (CuZnSOD; SOD1) on structure and function of cerebral arterioles.
  
  
  METHODS
  Systemic arterial pressure (SAP) and cross-sectional area of the vessel wall (CSA) and superoxide (O2-) levels (relative fluorescence of ethidium [ETH]) were examined in maximally dilated cerebral arterioles in mice with targeted disruption of one (+/-) or both (-/-) genes encoding CuZnSOD. Wild-type littermates served as controls. Vasodilator responses were tested in separate groups of mice.
  
  
  RESULTS
  CSA and ETH were significantly increased (P<0.05) in both CuZnSOD+/- and CuZnSOD-/- mice (CSA=435+/-24 and 541+/-48 microm2; ETH=18+/-1 and 34+/-2%) compared with wild-type mice (CSA=327+/-28 microm2; ETH=6%). Furthermore, the increases in CSA and ETH relative to wild-type mice were significantly greater (P<0.05) in CuZnSOD-/- mice than in CuZnSOD+/- mice (CSA=108 versus 214 microm2; ETH=12 versus 28%). In addition, dilatation of cerebral arterioles in response to acetylcholine, but not nitroprusside, was reduced by approximately 25% in CuZnSOD+/- (P<0.075) and 50% in CuZnSOD-/- mice (P<0.05) compared with wild-type mice.
  
  
  CONCLUSIONS
  Cerebral arterioles in CuZnSOD+/- and CuZnSOD-/- mice undergo marked hypertrophy. These findings provide the first direct evidence in any blood vessel that CuZnSOD normally inhibits vascular hypertrophy suggesting that CuZnSOD plays a major role in regulation of cerebral vascular growth. The findings also suggest a gene dosing effect of CuZnSOD for increases in O2-, induction of cerebral vascular hypertrophy and impaired endothelium-dependent dilatation.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. g-baumbach@uiowa.edu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Baumbach
authors.forename: Sean P
authors.initials: SP
authors.lastname: Didion
authors.forename: Frank M
authors.initials: FM
authors.lastname: Faraci
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply*; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006861:Hydrogen Peroxide / Q000378:metabolism; D006984:Hypertrophy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D009569:Nitric Oxide; D004492:Edetic Acid; D006861:Hydrogen Peroxide; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000109:Acetylcholine