88-OR

Abstract

Objectives Research on the pathogenesis and treatment of preeclampsia is hindered by lack of animal models. Here, we tested the hypothesis that the Dahl Salt Sensitive (Dahl S) rat, a known model of hypertension and kidney disease, is also a spontaneous model of preeclampsia. Methods We compared pregnancy in the Dahl S to a normotensive control rat strain, Sprague Dawley (SD), and another model of genetic hypertension with normal cardiovascular adaptations to pregnancy, the Spontaneously Hypertensive Rat (SHR). Female rats were implanted with telemetry units (DSI) via the femoral artery, allowed to recover for 10 days, and then mated with males of their same strain. Uterine artery resistance index (UARI) was measured on gestational day (GD) 18 via Doppler ultrasound (Vevo770) in anesthetized animals (n = 5–12), and urine was collected via metabolic cage on GD19. Rats were euthanized on GD20, pups were measured, the number of fetal resorptions was noted, and placentas were harvested for further analysis. Results Mean arterial pressure (MAP), proteinuria, and UARI were significantly greater at late pregnancy in the Dahl S rat compared to SD and SHR (Table). In the control strains, MAP decreased during pregnancy as expected, but there was a rise in MAP in the Dahl S. Pup and litter sizes were significantly smaller in the Dahl S rat, with an increased number of fetal resorptions in the Dahl S rat, indicating intrauterine growth restriction is present in this strain (Table). Conclusions These data suggest that the Dahl S rat exhibits a superimposed preeclamptic phenotype during pregnancy that is distinctive from preexisting hypertension during pregnancy as seen in the SHR control. Strain MAP (mmHg) Δ MAP (mmHg) Proteinuria (g/day) UARI # of Pups per Litter Pup weight/maternal weight (g/kg) Percent fetal resorptions SD 94 ± 2.2 −10.9 ± 2.1 11.0 ± 5.9 0.50 ± 0.01 13.3 ± 1.9 10.9 ± 0.3 0 SHR 114 ± 10.7∗ −20.3 ± 10.5 4.2 ± 3.2 0.53 ± 0.04 11.2 ± 0.6 8.3 ± 0.3 0 Dahl S 166 ± 3.0∗# 8.6 ± 2.4∗# 253.7 ± 28.2∗# 0.71 ± 0.02∗# 6.5 ± 1.6∗ 6.7 ± 0.8∗ 17.1 ± 6.5∗# ∗p Disclosures E.E. Gillis: None. J.N. Mooney: None. M.R. Garrett: None. J.M. Sasser: None.