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254: Effect of postnatal stress on the altered fetal programming of vascular function

      Objective

      We have previously shown that heterozygous mice offspring born to transgenic mothers lacking endothelial nitric oxide synthase (NOS3) have altered vascular function in later life compared to offspring born to wild type mothers. Our objective in the current study was to determine the effect of postnatal stress on the altered vascular function in this animal model of fetal programming.

      Study Design

      Homozygous NOS3 knockout (KO) and wild type mice (WT) were cross-bred to produce maternally-(KOM) and paternally-derived heterozygous (KOP) litters (n=10-12 per group). Offspring from both groups were stressed by placing them in a special caging system attached to a shaking platform that provided programmed intermittent shaking. Animals were sacrificed at 14 weeks of age, and the carotid arteries were prepared for in vitro vascular reactivity. Vascular responses to cumulative concentrations of phenylephrine (PE), in the presence and absence of the non-selective NOS inhibitor (L-NAME) were determined. Response following stress were compared with those obtained in similar unstressed offspring. ANOVA followed by Neuman-Keuls post hoc test were used for statistical analysis (significance: P<0.05).

      Results

      KOM mice offspring had significantly higher contractile responses to PE before and after L-NAME incubation when compared to KOP. However, the difference in these contractile responses between KOP and KOM was significantly less at every PE concentration when animals were stressed compared to non-stressed animals (figure).

      Conclusion

      Postnatal stress decreases the difference in vascular function induced by fetal programming. This is largely the result of worsening the vascular function in the normal offspring. The effects of postnatal stress appear to parallel the fetal programming effects of an adverse uterine environment.