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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. 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.

journal_name

Am J Obstet Gynecol

journal_title

American journal of obstetrics and gynecology

authors

Clark SM,Makhlouf M,Hankins GD,Anderson GD,Saade GR,Longo M

doi

10.1016/j.ajog.2007.01.031

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

354.e1-7

issue

4

eissn

0002-9378

issn

1097-6868

pii

S0002-9378(07)00142-1

journal_volume

196

pub_type

杂志文章

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