title: The role of oxidative stress in the developmental origin of adult hypertension.
abstract: OBJECTIVE
  To determine whether oxidative stress plays a role in the development of hypertension using a mouse model of fetal programming induced by endothelial nitric oxide synthase deficiency.
  
  
  METHODS
  Homozygous nitric oxide synthase knockout and wild type mice were cross-bred producing maternal (endothelial nitric oxide synthase+pat/-mat) and paternal (endothelial nitric oxide synthase+mat/-pat) heterozygous offspring. RNA from liver and kidney tissues of female pups were obtained at 14 weeks of age. Relative expression of the heat shock protein-B6, peroxiredoxin-3, superoxide dismutase-1, peroxisome proliferator-activated receptor gamma, nitric oxide synthase-1 and -2 were determined.
  
  
  RESULTS
  In the kidneys, expression of nitric oxide synthase-2, peroxiredoxin-3, heat shock protein-B6, and superoxide dismutase-1 was up-regulated in endothelial nitric oxide synthase+pat/-mat but not in endothelial nitric oxide synthase+mat/-pat compared with wild type offspring. In the liver, there were no significant differences in the expression of nitric oxide synthase-1, nitric oxide synthase-2, peroxiredoxin, superoxide dismutase-1, or peroxisome proliferator-activated receptor gamma; however, heat shock protein-B6 was down-regulated in both heterozygotes offspring compared with wild type.
  
  
  CONCLUSIONS
  The intrauterine environment alters oxidative pathways gene expression in the kidneys of offspring, which may be a mechanism in the development of adult hypertension.
authors.affiliation: Department of Obstetrics and Gynecology, American University of Beirut, Beirut, Lebanon.
authors.forename: Labib M
authors.initials: LM
authors.lastname: Ghulmiyyah
authors.forename: Maged M
authors.initials: MM
authors.lastname: Costantine
authors.forename: Huaizhi
authors.initials: H
authors.lastname: Yin
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Clark
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology*; D007668:Kidney / Q000196:embryology*; D008098:Litter Size; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D006360:Heat-Shock Proteins; D017382:Reactive Oxygen Species; D052247:Nitric Oxide Synthase Type II; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1