Abstract 028: Sex Differences In Hypertension And Cerebral Oxidative Stress Of Preeclamptic Rat Offspring

Abstract

Intrauterine growth restriction (IUGR) occurs when the fetus doesn’t receive adequate nutrients. The leading cause of IUGR is placental ischemia, often seen in preeclampsia (PE). Adult IUGR offspring have an increased risk of HTN and oxidative stress (OS), with sex differences. Studies have shown that IUGR males have HTN, cerebrovascular dysfunction (CVD), and cerebral OS at 17 wks; IUGR females are NT with limited CVD and no significant OS. Our study aims to characterize the sex differences in timing and changes of cerebral OS in IUGR offspring. HTN and OS are both present in adult IUGR males, however, the order and timing is unknown. We hypothesize that OS leads to HTN. To test this, we examined the changes in brain OS in 12 wk IUGR and control (CON) males (before HTN), and 17 wk IUGR males (which have HTN) vs CON males. We investigated the same time points in NT females. We divided pups from normal pregnant and PE Sprague-Dawley rats into groups based on pregnancy status and sex. Pups were aged to 12 and 17 wks. We collected brains to measure OS via western blot (Manganese superoxide dismutase) and colorimetric assays: hydrogen peroxide (H 2 O 2 ) and total antioxidant capacity (TAC). 12 wk IUGR and CON offspring were NT with no changes between groups or sex. There were no changes in cerebral H 2 O 2 , TAC, and MnSOD for IUGR offspring compared to their CON. At 17 wks, IUGR males had elevated mean arterial pressure (MAP; 143.0 ± 1.7 vs 133.0 ± 2.7 mmHg; p < 0.01). IUGR females were NT. Cerebral H2O2 levels in IUGR males were elevated (20.5 ± 8.0 vs 3.7 ± 1.0 uM/ mg Protein; p < 0.05) and unchanged in IUGR females. TAC in IUGR males was decreased (157.7 ±21.9 vs 234.9 ± 22.0 mM Trolox/mg Protein; p < 0.05) and unchanged in IUGR females. MnSOD was elevated in females with no differences between groups (150.4 ± 3.8 vs 110.9 ±7.1 IU/Protein/CON%; p < 0.002). All 12 wk rats were NT with no changes in cerebral OS. At 17 wks, IUGR males were HTN with elevated cerebral OS, with no changes in females. The lack of increase in OS at 12 wks, suggest that it’s not a precursor to HTN in males, but rather OS is a downstream effect from HTN. Future studies will look at factors that contribute to HTN and CVD in in IUGR offspring. Studies will also examine why 17 wk female IUGR are protected from HTN and cerebral OS.