title: Endothelial superoxide production is altered in sheep programmed by early gestation dexamethasone exposure.
abstract: BACKGROUND
  Animal models have demonstrated that maternal undernutrition or early gestation glucocorticoid exposure induces endothelial dysfunction in the offspring.
  
  
  OBJECTIVE
  We sought to determine whether early gestation dexamethasone (DEX) exposure is further associated with increased vascular superoxide anion production.
  
  
  METHODS
  DEX (0.28 mg/kg/day i.v. for 48 h) was administered to pregnant ewes at 27-28 days' gestation (term 145 days). Tissues were harvested from DEX-exposed and control lambs at 125 days' gestation (n = 6 for each group) and 4 months following delivery (n = 9 and 12, respectively).
  
  
  RESULTS
  By lucigenin-enhanced chemiluminescence, coronary and mesenteric arteries from DEX-exposed fetuses exhibited diminished basal superoxide production (both p < 0.01). Similarly, DEX-exposed carotid arteries from 4-month-old lambs had decreased superoxide production (p < 0.01) that localized to the endothelium by endothelial cell culture and dihydroethidium fluorescence. In contrast, DEX-exposed coronary arteries from the 4-month-old sheep had increased superoxide production (p < 0.05). Although early gestation DEX exposure did not alter lipid peroxidation, DEX exposure was associated with significantly increased renal and cerebral cortex aconitase activity (consistent with decreased protein oxidation). These changes occurred in the absence of alterations in renal cortex superoxide dismutase activity.
  
  
  CONCLUSIONS
  We conclude that in a DEX-exposure model of fetal programming, endothelial superoxide production and protein oxidation are decreased in the mesenteric and carotid circulation. This contrasts with the postnatal coronary artery-specific increase in superoxide production.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. robert-roghair@uiowa.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Miller
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Scholz
authors.forename: Fred S
authors.initials: FS
authors.lastname: Lamb
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D015227:Lipid Peroxidation; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017382:Reactive Oxygen Species; D012756:Sheep / Q000196:embryology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D005938:Glucocorticoids; D017382:Reactive Oxygen Species; D013481:Superoxides; D003907:Dexamethasone; D013482:Superoxide Dismutase