Document Detail


Transgenerational effect of fetal programming on vascular phenotype and reactivity in endothelial nitric oxide synthase knockout mouse model.
MedLine Citation:
PMID:  18771972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The objective of the study was to investigate the transgenerational effect of fetal vascular programming
STUDY DESIGN: Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO-/-) mothers lacking a functional NOS3 (KOM) vs wild-type control mothers (KOP). The first-generation KOM(+/-) and KOP(+/-) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in vitro vascular reactivity studies.
RESULTS: WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic blood pressure, mean arterial pressure, and pulse pressure, compared with WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE), compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared with female. Acetylcholine responses were decreased in female KOM-F2WT, compared with female KOP-F2WT, but the difference was not statistically significant
CONCLUSION: Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.
Authors:
Maged M Costantine; Labib M Ghulmiyyah; Esther Tamayo; Gary D V Hankins; George R Saade; Monica Longo
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  199     ISSN:  1097-6868     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-05     Completed Date:  2008-10-30     Revised Date:  2011-04-01    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  250.e1-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0144, USA. mmcostan@utmb.edu.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Blood Pressure / genetics,  physiology*
Body Weight
Female
Fetal Development / genetics,  physiology*
Male
Mice
Mice, Knockout
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase / deficiency
Phenotype
Vasoconstriction / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
R01 HL080558-02/HL/NHLBI NIH HHS; R01 HL080558-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
50903-99-6/NG-Nitroarginine Methyl Ester; EC 1.14.13.39/Nitric Oxide Synthase
Comments/Corrections

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