Abstract 090: Increased Uterine Artery Resistance Index Results In Placental Hypoxia And Tnf-α In The Dahl Salt Sensitive Rat During Pregnancy

Abstract

In normal pregnancy, uterine artery resistance index (UARI) decreases as pregnancy progresses to accommodate the increased blood supply to the growing fetus. In preeclampsia, increased UARI impedes the utero-placental blood flow. Recent studies in our lab indicate that the Dahl salt sensitive (S) rat spontaneously develops a preeclamptic phenotype, characterized by increased blood pressure and proteinuria as pregnancy progresses and a decrease in litter and pup size. Here, we tested the hypothesis that the phenotype in the Dahl S rat is due to decreased placental blood flow, causing the placenta to become hypoxic, resulting in increased production of TNF-α. Female Dahl S and Sprague Dawley rats were mated with males of their same strain, and pregnancy was confirmed by presence of sperm (D1). UARI was measured during mid and late pregnancy (D14 and 18, respectively) via Doppler ultrasound in anesthetized animals (n= 4-12). Rats were sacrificed on D20, and placentas were harvested for further analysis. TNF-α and HIF-1α were measured in homogenized placentas via commercially available ELISA (n= 5) and Western Blot analysis (n= 9-11), respectively. UARI decreased in the Sprague Dawley rat between D14-18, but increased in the Dahl S rat (Table). HIF-1α was significantly increased in the Dahl S placenta vs Sprague Dawley (Table), and TNF-α also showed a tendency to increase in the Dahl S placenta (p=0.08). These data suggest that the relative decrease in blood flow to the placenta during pregnancy in the Dahl S rat causes a hypoxic environment, leading to the release of vasoactive factors that contribute to the development of the preeclamptic phenotype observed in this strain.