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48: Fetal programming of adult blood pressure in a mouse model of adverse uterine environment induced by nitric oxide synthase 3 (NOS3) deficiency: Effect of postnatal stress

      Objective

      Nitric oxide and NOS3 are critical in the regulation of utero-placental perfusion. We have previously shown that heterozygous mice offspring born to transgenic mothers lacking NOS3 have systolic hypertension in later life compared to offspring born to wild type mothers. Our objective was to determine whether the cardiovascular response to stress is also altered in this animal model of fetal programming.

      Study Design

      NOS3 knockout and wild type mice were cross-bred to obtain maternally-derived (KOM) and paternally-derived (KOP) heterozygous offspring. At 14 weeks of age, blood pressure (BP) catheters were inserted through the left carotid artery into the aortic arch. BP was recorded continuously for 6 days by telemetry in the conscious unrestrained offspring. Stress was induced by placing the mice in a caging system attached to a shaking platform that provided intermittent shaking between the 3rd and 4th day of recording. Mean BP (MBP), pulse pressure (PP), systolic BP (SBP) and diastolic BP (DBP) were analyzed. Student t-test was used for statistical analysis (significance: p<0.05).

      Results

      As previously reported without stress, KOM mice offspring had significantly higher MBP and PP compared with KOP. This difference was accentuated following stress. Compared with KOP, DBP in KOM before stress was not significantly different, but became significantly higher after stress (Figure).

      Conclusion

      The adverse uterine environment in the NOS3 knockout mice leads to systolic hypertension in the adult offspring, which is further compounded by diastolic hypertension in response to postnatal stress.
      Supported by NHLBI R01 HL080558-02