Progesterone supplementation attenuates hypertension and the autoantibody to the angiotensin II type I receptor in response to elevated interleukin-6 during pregnancy.

OBJECTIVE: Preeclampsia is a multisystem disorder recognized as hypertension with proteinuria developing >20 weeks' gestation. Preeclampsia is associated with chronic immune activation characterized by increased T and B lymphocytes, cytokines, and antibodies activating the angiotensin II type I receptor (AT1-AA). Hypertension in response to elevated interleukin (IL)-6 during pregnancy occurs with increased renin activity and AT1-AA, and reduced kidney function. STUDY DESIGN: We aim to determine whether 17-alpha-hydroxyprogesterone caproate (17-OHPC), progesterone, improved inflammatory pathways during elevated IL-6 in pregnant rats. IL-6 (5 ng/d) was infused via miniosmotic pumps into normal pregnant (NP) rats beginning on day 14 of gestation and 17-OHPC (3.32 mg/kg) was diluted in normal saline and injected on day 18. Blood pressure (mean arterial pressure [MAP]) determination and serum collection were performed on day 19 of gestation. RESULTS: MAP in NP was 100 ± 3 mm Hg, which increased with IL-6 to 112 ± 4 mm Hg (P < .05). Pregnant rats given 17-OHPC alone had a MAP of 99 ± 3 mm Hg and MAP increased to 103 ± 2 mm Hg in IL-6+17-OHPC. AT1-AA was 1.2 ± 0.5 bpm in NP rats, increased to 17 ± 9 bpm with IL-6 infusion but administration of 17-OHPC significantly blunted AT1-AA to 4 ± 0.8 bpm in NP+IL-6+17-OHPC. Total circulating nitrate/nitrite was significantly decreased and placental Ser(1177)-phosporylated-eNOS/eNOS was lowered with IL-6 infusion. Supplementation of 17-OHPC significantly improved placental Ser(1177)-phosporylated-eNOS/eNOS however, circulating nitrate/nitrite was unchanged with 17-OHPC supplementation. CONCLUSION: This study illustrates that 17-OHPC attenuated hypertension, decreased AT1-AA activity, and improved placental nitric oxide in response to elevated IL-6 during pregnancy and could lend hope to a new potential therapeutic for preeclampsia.

Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia.

OBJECTIVE: Preeclampsia (PE) is associated with hypertension and elevated endothelin (ET-1), an indicator of endothelial cell activation and dysfunction. Reduction of uteroplacental perfusion (RUPP) in the pregnant rat model of PE is characterized by elevated mean arterial pressure, inflammatory cytokines, and activation of the ET-1 system. We aim to determine whether 17-alpha-hydroxyprogesterone caproate (17-OHPC) or progesterone suppresses these pathways. STUDY DESIGN: Plasma progesterone was purified from normal pregnant (NP) and PE patients and measured via enzyme-linked immunosorbent assay. Human umbilical vein endothelial cells were exposed to the sera with or without progesterone added and ET-1 was measured. Pregnant rats underwent the RUPP procedure with or without intraperitoneal 17-OHPC. Mean arterial pressure was compared in RUPP vs NP rats. Human umbilical vein endothelial cells were exposed to NP or RUPP sera, with and without progesterone and ET-1 measured. RESULTS: Progesterone was significantly decreased in PE women compared with NP women. In response to human sera, ET-1 was elevated in PE women compared to NP women, and decreased with addition of progesterone. Mean arterial pressure was significantly elevated in RUPP vs NP rats but was attenuated by 17-OHPC. ET-1 secretion was stimulated significantly by RUPP compared to NP rat sera, but attenuated by progesterone. CONCLUSION: Circulating progesterone is significantly lower in PE women compared to controls. 17-OHPC attenuates hypertension in response to placental ischemia in RUPP rats. Progesterone blunts vascular ET-1 stimulated at cellular level by sera from PE women or RUPP rats. Decreased circulating progesterone is associated with stimulation of ET-1. 17-OHPC supplementation blunts hypertension and progesterone blunts endothelial cell ET-1 secretion in response to placental ischemia.

Perinatal outcome associated with sonographically detected globular placenta.

OBJECTIVE: To evaluate the association between the sonographic appearance of globular placenta and perinatal outcome. STUDY DESIGN: We prospectively followed the pregnancy course and perinatal outcome in women with globular placentas (hyperechoic, thick and highly vascular placentas with edges that lack the typical "tapering" appearance) during routine sonographic study. RESULTS: Fourteen women were included. In 7 women the globular appearance of the placenta normalized spontaneously, and perinatal outcome was good. The other 7 experienced poor perinatal outcomes. There were no significant differences between the 2 groups. Among pregnancies in which the globular placental appearance persisted, 3 resulted in fetal demise; 3 women had severe intrauterine growth restriction and oligohydramnios and underwent cesarean deliveries at 26, 27 and 31 weeks, respectively; and 1 patient had premature preterm rupture of membranes and underwent a cesarean delivery due to placental abruption. CONCLUSION: In half the pregnancies complicated by the sonographic appearance of a globular placenta, this shape spontaneously normalized, and the perinatal outcome was normal. However, when the globular appearance of the placenta persisted, the condition was associated with a poor perinatal outcome. Pregnancies complicated by a globular placenta should be followed closely.

Impedance cardiography assessed treatment of acute severe pregnancy hypertension: a randomized trial.

OBJECTIVE: Using noninvasive bedside impedance cardiography (ICG), we compared the effectiveness and the hemodynamic impact of intravenous labetalol versus hydralazine for the reduction of acute-onset severe hypertension to ACOG-recommended blood pressure levels (ACOG Committee Opinion 514). STUDY DESIGN: In this prospective randomized pilot study of acutely severe systolic hypertension (≥160 mmHg), pregnant women received either labetalol (L) or hydralazine (H) intravenously and underwent thoracic ICG before and after treatment. Data analysis were performed using STATA software (StataCorp LP, College Station, TX); data are expressed as mean ± SD. RESULTS: About 29 patients completed the study. There was no significant difference in mean arterial pressure (MAP) between groups [H = 119.4 mmHg, L = 117.7 mmHg, mean difference (MD) = 1.73); the estimated MD between baseline and follow-up ICG was -9.17 (p = 0.001, 95% CI: -14.39 to -3.95). There were no significant differences in total peripheral resistance (TPR) between groups (H = 1771.3, L = 1976.97, MD = 205.62) or cardiac output (CO) between groups (H = 5.7, L = 5.1, MD = 0.64) or a significant MD between these at baseline and follow-up. CONCLUSION: Both drugs performed similarly to achieve ACOG-recommended initial blood pressure reduction safely without side effects or excessive acute hemodynamic profile correction toward normal pregnancy values.

Antenatal sonographic diagnosis of massive subchorionic hematoma: a case report.

BACKGROUND: Massive subchorionic hematoma (MSH), described by Breus in 1892 (Breus mole), is a rare but serious condition in pregnancy in which a large amount of blood, mainly maternal, collects and dissects the chorionic plate from the villous chorion. CASE: A case of MSH was complicated by intrauterine growth retardation (IUGR) and intrauterine fetal death at 23 weeks' gestation. Pregnancy was complicated by advanced maternal age and chronic hypertension. There was no antenatal vaginal bleeding. Ultrasound at 19 weeks showed a small-for-gestational-age fetus, echogenic bowel and globular placenta. Amniocentesis revealed a normal male karyotype. At 23 weeks the patient presented with vaginal spotting, cramping and absent fetal heart tones. Labor was induced with misoprostol, and vaginal delivery occurred. The placenta showed an organized thrombus adherent to the chorionic plate, and a large subchorionic hematoma comprised at least half the disc volume. CONCLUSION: Antenatal sonographic diagnosis of MSH and IUGR can be achieved.

Endothelin-1 is not a Mechanism of IL-17 Induced Hypertension during Pregnancy.

Preeclampsia is characterized as new onset maternal hypertension and proteinuria after 20 weeks gestation. Studies suggest that endothelin (ET-1) is a regulator of vascular function in preeclampsia and plays a major role in mediating chronic reduction in uterine perfusion pressure (RUPP)-induced hypertension. We recently demonstrated a role for the autoimmune cytokine interleukin 17 (IL-17) in causing placental oxidative stress and hypertension during pregnancy. In this current study, we investigated the role of ET-1 as a potential mechanism by which TH17 cells and IL-17 mediate hypertension in preeclampsia. While IL-17 infusion into normal pregnant rats increased blood pressure in a dose-responsive manner (98+/-2 mmHg in NP (n=20) to 105+/-3 mmHg in IL-17 (50pg/day, n=20) to 120+/-4 mmHg in IL-17 (100pg/day, n=10) to 123+/-3 mmHg in IL-17 (150 pg/day, n=7), it decreased local endothelin in placentas (NP (n=10) 7.5±0.3; IL-17 (100 pg/day, n=5) 6.4±0.2; IL-17 (150 pg/day, n=12) 4.5+1.5) and renal cortices (NP (n=8) 7.9 + 0.4; IL-17 (100 pg/day, n=6) 7.1±0.4; IL-17 (150 pg/day, n=4) 1.6 +0.7 during pregnancy. In addition, increasing IL-17 directly reduced secretion of ET-1 by human umbilical venous endothelial cells (HUVECs). HUVEC ET-1 secretion decreased from that seen in serum free media 42.7±7.7 pg/ml to 36.2 ± 5.9 pg/ml at 10 pg IL-17 to 31.3 ± 5.1 pg/ml at 10 µg IL-17. Our observations suggest that IL-17 negatively regulates the ET-1 pathway in local tissues and cultured endothelial cells and that the ET-1 pathway is not a mechanism by which IL-17 causes hypertension during pregnancy.