Transgenerational effect of fetal programming on vascular phenotype and reactivity in endothelial nitric oxide synthase knockout mouse model.
OBJECTIVE
The objective of the study was to investigate the transgenerational effect of fetal vascular programming


METHODS
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


CONCLUSIONS
Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.
Costantine
Maged M
MM
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0144, USA. mmcostan@utmb.edu.
Ghulmiyyah
Labib M
LM
Tamayo
Esther
E
Hankins
Gary D V
GD
Saade
George R
GR
Longo
Monica
M
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology*; D001835:Body Weight; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000172:deficiency; D010641:Phenotype; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
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