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

Shannon M. Clark, Michel Makhlouf, Gary D.V. Hankins, Garland D. Anderson, George R. Saade, Monica Longo

Research output: Contribution to journalArticle

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)354.e1-354.e7
JournalAmerican journal of obstetrics and gynecology
Issue number4
StatePublished - Apr 2007



  • cross-fostering
  • fetal programming
  • hypertension
  • vascular reactivity

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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