Abstract 049: Preeclampsia in the Dahl Salt Sensitive Rat is Associated with Increased Uterine Artery Resistance and Reduced Placental Microvascular Density

Abstract

We showed that the Dahl salt sensitive (Dahl S) rat is a spontaneous model of preeclampsia superimposed on chronic kidney disease and hypertension. This model exhibits intrauterine growth restriction, decreased pup weight, increased fetal death, and placental hypoxia; however, the underlying mechanisms are unknown. We hypothesized that a pathological remodeling and rarefaction in the maternal placental bed drives the development of preeclampsia in this model. Pregnant Dahl S and Sprague-Dawley (SD) rats were used in this study. Uterine artery resistance index (UARI) was calculated via Doppler ultrasound (Vevo 770) on day 18 of pregnancy (UARI=(peak systolic flow velocity - end diastolic flow velocity)/ peak systolic flow velocity). On day 20 of pregnancy, placentas were perfused through the uterine circulation with a silicon-polymer contrast (Microfil MV122). Individual placentas were then excised, scanned using a micro-CT scanner (SkyScan 1076), and 3D reconstructed for analysis and quantification of the placental vasculature on the maternal side. Microvascular density was calculated for vessels of diameters in the 0-500 μm ranges. UARI was higher in the Dahl S compared to the SD (0.71±0.02 vs 0.51±0.02, n=4-12, p<0.05). Density of placental microvessels in the 200-500 μm range was significantly decreased in placentas from Dahl S rats, and we observed a strong trend towards a decrease in density of microvessels in the 0-200 μm range (n=3-5, Figure). These results suggest that the impaired fetal growth and placental hypoxia in the Dahl S rat may be mediated by insufficient placental vascularization and reduced blood flow to the feto-placental unit.