Early Administration of 17‐Hydroxyprogesterone Caproate to Reduced Uterine Perfusion Pressure (RUPP) Rat Model of Preeclampsia Improves Inflammation, Uterine artery Vasoconstriction and Blood Pressure During Pregnancy

Abstract

Preeclampsia (PE) is characterized by new onset hypertension and increased uterine artery resistance (UARI), elevated TNF-α, sFlt-1, and decreased of nitric oxide (NO) bioavailability during pregnancy. 17-hydroxyprogesterone caproate (17-OHPC) is approved for cessation of preterm labor in pregnancies not complicated by PE. Therefore, we hypothesized that 17-OHPC administered on day 15 of gestation into RUPP rats could reduce blood pressure (MAP), TNF-α, sFlt-1, UARI, and increase pup weight and NO bioavailability. Carotid catheters were inserted on day 18. MAP, blood and tissues were collected on day 19. MAP in normal pregnant (NP) rats (n=9) was 92 +1.35, 126 +1.98 in RUPP rats (n=17) and 111+1.54 mmHg in RUPP+17-OHPC (n=13), p <0.05. Pup weight was 2.31+0.12 in NP (n=13), 1.88+ 0.05 in RUPP rats (n=24), which improved to 2.01+0.07 grams in RUPP+17-OHPC (n=15), p <0.05. UARI was 0.79+0.03 in RUPP rats (n=4) and 0.59+0.04 in RUPP+17-OHPC (n=5), p<0.05. Plasma levels of TNFα, sFlt1 were 64.0+14.1, 385.9+141 in RUPP rats (n=7), which were blunted to 17.8+9.6, 110.2+11.1 pg/mL in RUPP+17OHPC (n=5), p<0.05. Plasma NOx was 10.82+2.3 in RUPP rats (n=13) but was improved to 25.5+5.2 µM in RUPP+17-OHPC (n=5), p<0.05. In conclusion, early administration of 17-OHPC improves TNF-α, sFtl-1, UARI, hypertension, pup weight and nitric oxide bioavailability in response to placental ischemia and should be considered for addition to the management of severe preterm PE. NIH RO1HD067541, T32HL105324