Abstract 093: Progesterone Supplementation Improves Blood Pressure And Uterine Artery Resistance In Response To Placental Ischemia During Pregnancy

Abstract

Preeclampsia (PE), new onset hypertension at 20 weeks of gestation, is characterized by increased uterine artery resistance index (UARI), chronic immune activation and decreased of vasodilators such as nitric oxide (NO). Despite being one of the leading causes of death in pregnant women, currently there is no effective treatment for PE except for early delivery of the fetus. We have demonstrated that PE women have significantly lower circulating progesterone than normal pregnant (NP). 17-alpha-hydroxyprogesterone caproate (17-OHPC) is a synthetic metabolite of progesterone used for the prevention of recurrent preterm birth and although the mechanism is not understood, is suspected to have vasodilatory and anti-inflammatory effects. Therefore, we hypothesized that progesterone (17-OHPC) supplementation could reduce blood pressure (MAP), pro-inflammatory cytokines, CD4+ T cells, UARI, as well as increase NO bioavailability in a hypertensive rat model of PE. To address this question 17-OHPC (3.32mg/kg) was intraperitoneally administered on day 18 of gestation into Reduced Uterine Perfusion Pressure (RUPP) rats and carotid catheters were inserted. MAP, blood and tissues were collected on day 19. MAP in NP rats (n=13) was 92±2; 123±2 in RUPP (n=18), and 116 ±1 mmHg in RUPP+17-OHPC (n=10), p <0.05. UARI was 0.78±0.03 in RUPP (n=4) and 0.63±0.038 in RUPP+17-OHPC (n=8), p<0.05. Circulating CD4+ T cells were 1.19±1.0% of gated cells in NP (n=7), which increased to 8.52±2.4% in RUPP rats (n=10) but was significantly reduced to 2.72±0.87% (n=14) in RUPP + 17 O-HPC, p <0.05. Total circulating nitrate/nitrite was 26.34 ±3.5 μM in NP (n=12); 14.58±3.1 in RUPP rats (n=8) and increased to 26.69±1.62 in RUPP+17-OHPC (n=7), p <0.05. Aortic eNOS expression was 0.65±0.11 A.U in NP (n=4), which decreased to 0.33±0.01 in RUPP rats (n=4) but increased to 0.57±0.01 in RUPP+17-OHPC (n=5), p <0.05. Levels of TNF-alpha were 65.84±17.7 pg/ml in RUPP rats (n=5) but were blunted to 17.24±3.9 in RUPP+17-OHPC (n=8), p <0.05. In conclusion, 17-OHPC supplementation improves inflammation, UARI, hypertension, and nitric oxide bioavailability in response to placental ischemia during pregnancy and should therefore be considered further for addition to the clinical management of PE