55-OR

Abstract

Objectives 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). 17-alpha-hydroxyprogesterone caproate (17-OHPC) is a synthetic metabolite of progesterone used for the prevention of recurrent preterm birth. The objective of this study was to determine whether 17-OHPC could reduce blood pressure (MAP), inflammation, UARI, as well as increase NO bioavailability in a hypertensive rat model of PE. Methods 17-OHPC (3.32 mg/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. Results 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). UARI was 0.78 ± 0.03 in RUPP ( n = 4) and 0.63 ± 0.038 in RUPP + 17-OHPC ( n = 8). 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-OHPC. 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. 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). 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). Conclusions In conclusion, 17-OHPC improves inflammation, UARI, hypertension, and NO bioavailability in response to placental ischemia during pregnancy. Disclosures L.M. Amaral: None. D.C. Cornelius: None. J. Moseley: None. J.N. Martin: None. B. LaMarca: None.