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. 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.