The effect of the postnatal environment on altered fetal programming of adult vascular function in mice that lack endothelial nitric oxide synthase

Am J Obstet Gynecol. 2007 Apr;196(4):354.e1-7. doi: 10.1016/j.ajog.2007.01.031.

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.

Study design: 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.

Conclusion: Postnatal interventions may alter the adult vascular profile favorably that is the result of an abnormal intrauterine environment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / pharmacology
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Carotid Arteries / drug effects
  • Carotid Arteries / embryology*
  • Disease Models, Animal
  • Female
  • Fetal Development / genetics
  • Fetal Development / physiology
  • Heterozygote
  • Homozygote
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Litter Size
  • Mice
  • Mice, Knockout
  • Nitric Oxide Synthase / deficiency*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitric Oxide Synthase Type III
  • Phenylephrine / pharmacology
  • Pregnancy
  • Pregnancy, Animal
  • Probability
  • Random Allocation
  • Sensitivity and Specificity
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Phenylephrine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Acetylcholine