title: The effect of the postnatal environment on altered fetal programming of adult vascular function in mice that lack endothelial nitric oxide synthase.
abstract: OBJECTIVE
  The purpose of this study was to investigate vascular reactivity in heterozygous and homozygous offspring with a genetic predisposition for hypertension after postnatal cross-fostering to mothers with the opposite genetic inheritance of the NOS3 knockout allele.
  
  
  METHODS
  Homozygous NOS3 knockout (C57BL/6J-NOS3(-/-KO)) and wild-type mice (NOS3(+/+WT)) were bred to obtain heterozygous litters with a paternally derived (NOS3(+/-pat)) or maternally derived (NOS3(+/-mat)) knockout allele. After delivery, heterozygous and homozygous litters were cross-fostered to a mother with the opposite NOS3 gene status. Carotid arteries were placed in a wire myograph for isometric tension recording with the use of contractile and relaxant agents. Statistical analysis with 1-way analysis of variance and Neuman-Keuls post-hoc testing was performed.
  
  
  RESULTS
  Increased sensitivity to phenylephrine and absent relaxation to acetylcholine in NOS3(+/-mat) was reversed with cross-fostering, and vasorelaxation to isoproterenol was increased. Contraction to calcium was increased in the cross-fostered paternally derived and wild-type litters.
  
  
  CONCLUSIONS
  Postnatal interventions may alter the adult vascular profile favorably that is the result of an abnormal intrauterine environment.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA. shclark@utmb.edu
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Clark
authors.forename: Michel
authors.initials: M
authors.lastname: Makhlouf
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: Garland D
authors.initials: GD
authors.lastname: Anderson
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.forename: Monica
authors.initials: M
authors.lastname: Longo
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002339:Carotid Arteries / Q000187:drug effects / Q000196:embryology*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008098:Litter Size; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine