402: The effect of postnatal age on fetal vascular programming of blood pressure in a nitric oxide synthase knockout mouse model

To determine the effect of postnatal age on fetal vascular programming of adult blood pressure (BP) using a well characterized mouse model with abnormal uterine environment induced by lack of a functional endothelial nitric oxide synthase (NOS3), an important regulator of utero-placental perfusion. Homozygous NOS3 knockout (−/−KO) and wild type controls (+/+WT) were cross-bred to obtain heterozygous offspring (KOM) developing in KO mothers lacking a functional NOS3 versus genomically similar offspring (KOP) born to wild-type mothers having NOS3 gene. Male KOM and KOP offspring at 7 and 21 weeks of age were used for in vivo BP measurement by a telemetry system. A BP catheter was inserted into the aortic arch and BP monitored continuously for 8 days in the conscious unrestrained heterozygous offspring mice. The mean arterial pressure (MAP), systolic (SBP), diastolic (DBP), pulse pressure (PP) and heart rate (HR) were obtained. Their mean values over an 8 day period were calculated and Student t-test used for statistical analysis (significance: p < 0.05). BP in the KOM and KOP mice offspring at 7 weeks of age did not differ in any of the parameter considered. However, at 21 weeks the KOM offspring show a significant higher MAP (117.18 ± 1.6 vs 109.2 ± 0.9 mmHg), DBP (87.6 ± 2.3 vs 57.2 ± 5.6 mmHg) as well as PP and HR compared with the KOP offspring. Only SBP was not different between the two groups at 21 weeks. Heterozygous offspring born to a mother with an adverse uterine environment due to lack of NOS3 have altered BP compared with their genomically similar counterparts developing in a normal mother. The effect of fetal programming on blood pressure is not evident in early postnatal life. Early screening and intervention may present an opportunity to prevent onset of cardiovascular disease later in life.