(722) Progesterone supplementation in preeclamptic women reduces blood pressure and inflammatory mediators of hypertension during pregnancy

Introduction: Preeclampsia (PE), new onset hypertension after 20 weeks of gestation, is associated with lower progesterone, increased CD4+T cells, inflammatory cytokines, and autoantibodies to angiotensin II type 1 receptor (AT1-AA). We have previously shown that placental PE CD4+ T cells cause a PE phenotype in athymic nude rats. Moreover, we have shown that 17-hydroxyprogesterone caproate (17-OHPC), lowers blood pressure in PE patients, however, it is unclear if this was mediated via a T cell effect.

Objective: Determine if placental CD4+ T cells from 17-OHPC treated PE women increase blood pressure in athymic nude recipient rats.


 

Study Design:

PE women received 17-OHPC (250 mg, I.M.) with blood draws before and after injection. One million placental CD4+ T cells from normal pregnant (NP) or PE participants were isolated by magnetic beads and injected I.P. into pregnant nude athymic rats on gestational day (GD) 12. On GD18, carotid catheters were inserted. On GD19, mean arterial blood pressure (MAP), blood and tissues were collected. One-way ANOVA was used for statistical analysis.


Results: Participants had matched GA. Maternal blood pressure was 116 +/-4 mmHg in NP women (n=8), 147 +/- 4 mmHg in PE women (n=19) and reduced to 136 +/- 3 mmHg in PE+17-OHPC women (n=14, p< 0.05). AT1-AAs were 23 +/- 5 beats per minute in PE (n=4) and 10 +/-2 in PE+17-OHPC (n=8; student t-test, p< 0.05). Placental CD4+T cells were 2+/- 1% gate in NP, 6 +/- 1 in PE, and 3 +/-1 % gate in PE+17-OHPC (n=4-5). Circulating TNF-α was 21 +/- 4 pg/mL in NP, 41 +/-8 in PE (p< 0.05), 21+/-5 pg/ml in PE+17-OHPC (n=6-8, p< 0.05). In pregnant nude recipient rats, MAP was 98 +/- 2 mmHg with NP CD4+ T cells (n=5), 122 +/-7 (n=7, p< 0.05) with PE CD4+ T cells (n=7) and 102+/- 5 with PE+17-OHPC CD4+ T cells (n=7, p< 0.05).

Conclusion: 17-OHPC in PE women reduces blood pressure and inflammatory mediators of hypertension during pregnancy. Moreover, PE CD4+ T cells treated with 17-OHPC do not mediate a PE phenotype in recipient pregnant rats.