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


METHODS
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.


CONCLUSIONS
Postnatal interventions may alter the adult vascular profile favorably that is the result of an abnormal intrauterine environment.
Clark
Shannon M
SM
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch at Galveston, Galveston, TX 77550, USA. shclark@utmb.edu
Makhlouf
Michel
M
Hankins
Gary D V
GD
Anderson
Garland D
GD
Saade
George R
GR
Longo
Monica
M
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002339:Carotid Arteries / Q000187:drug effects / Q000196:embryology*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008098:Litter Size; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine