endothelin-1 and Eclampsia

The activation of neutrophils was studied in preeclampsia (n = 10) and eclampsia (n = 20) compared to normotensive controls (n = 10) and nonpregnant essential hypertensives (n = 10). Plasma elastase levels were raised in preeclampsia (0.53 +/- 0.32 microgram/mL, P < .002) and eclampsia (1.26 +/- 0.8 microgram/mL, P < .001) respectively compared to normal pregnancies (0.032 +/- 0.009 microgram/mL). The plasma elastases were more elevated in eclamptic cases compared to essential hypertensive (0.53 +/- 0.27 microgram/mL; P = .01) patients. We analyzed the correlation among elastase values, systolic (SBP), mean blood pressures (MBP), endothelin-1 (ET-1) levels and sera cytotoxicity (as measured by fura-2 release from human umbilical venous endothelial cell culture) in eclamptic cases. SBP and MBP were significantly correlated with plasma elastase levels in preeclampsia (r = 0.67, 0.63, respectively; P < .03) and eclampsia (r = 0.49, 0.49, respectively; P < .02). ET-1 levels were correlated with SBP (P = .003) and MBP (P = .001) and corresponding elastase levels (r = 0.606, P < .003) in eclamptic patients. Doses of 10, 25, and 50 pmol/mL of ET-1 increased elastase release in human neutrophil cultures dose and time dependently. Cytotoxicity of eclamptic sera correlated (P < .001) to the corresponding plasma elastase values. Therefore, this study suggests that neutrophil activation and ET-1 induced neutrophil activation occurs in this disease.

Topics: Adult; Blood Pressure; Cell Survival; Cells, Cultured; Eclampsia; Endothelin-1; Endothelium, Vascular; Female; Fluorescent Dyes; Fura-2; Humans; Hypertension; Leukocyte Elastase; Neutrophil Activation; Neutrophils; Pancreatic Elastase; Pre-Eclampsia; Pregnancy

Preeclampsia is associated with innate inflammatory response resulting in elevated tumor necrosis factor-α, agonistic autoantibodies to the angiotensin II type I receptor, and activation of endothelin 1 (ET-1). This study was designed to determine the role of B-cell depletion, resulting in agonistic autoantibodies to the angiotensin II type I receptor suppression to mediate hypertension via activation of ET-1 in the placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. To achieve this goal we examined the effect of RUPP on mean arterial pressure and ET-1 in the presence and absence of chronically infused rituximab (R; 250 mg/kg), a B-lymphocyte-suppressive agent used clinically to treat autoimmune diseases. Mean arterial pressure was 103±1 mm Hg in normal pregnant (NP) rats; 103±3 mm Hg in NP+R versus 133±2 mm Hg in RUPP rats, and 118±2 mm Hg in RUPP+R rats (P<0.001 vs RUPP controls). B lymphocytes decreased from 6.0±0.5% gated cells in RUPP to 3.7±0.8% gated cells in RUPP+R rats. Importantly, agonistic autoantibodies to the angiotensin II type I receptor decreased from 18±1 bpm in RUPP rats to 10±1 bpm in RUPP+R rats. ET-1 decreased 1.5-fold in kidneys and 4-fold in the placenta (P<0.01) of RUPP+R versus RUPP rats. Media ET-1 excretion from endothelial cells exposed to serum from NP, RUPP, NP+R, or RUPP+R rats was determined. ET-1 from endothelial cells treated with NP serum was 53+13 pg/mg and increased to 75+10 pg/mg with RUPP serum. In contrast, ET-1 secretion decreased in response to B-cell-depleted RUPP serum to 50±8 pg/mg and was unchanged in response to NP+R sera (46±12 pg/mg). These data demonstrate the important roles that B-lymphocyte activation and agonistic autoantibodies to the angiotensin II type I receptors play in the pathophysiology of hypertension in response to placental ischemia.

Topics: Analysis of Variance; Animals; Antibodies, Monoclonal, Murine-Derived; Autoantibodies; B-Lymphocytes; Blood Pressure; Cells, Cultured; Eclampsia; Endothelial Cells; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Ischemia; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Reverse Transcriptase Polymerase Chain Reaction; Rituximab; Uterus

The aim of this study was to determine the effect of treatment on endotelin-1 concentration that is considered to have role in etiopathogenesis of eclampsia and preeclampsia.. Nine patients with eclampsia and 12 patients with preeclampsia were included to the study. Endothelin-1 levels were measured before and after magnesium sulfate treatment. After the magnesium sulfate administration, if the blood pressure was still elevated, nifedipine was given.. Endothelin-1 levels of preeclamptic patients before and after magnesium sulfate treatment were 16.9 +/- 2.3 fmol/ml and 14.6 +/- 1.9 fmol/ml respectively (p < 0.05). The same measurements of eclamptic patients were 18.1 +/- 3.2 and 14.7 +/- 3.4 respectively (p < 0.05). The mean blood pressures of preeclamptic patients before and after magnesium sulfate were 125.8 +/- 7.3 mm-Hg, 118.2 +/- 8.7 mm-Hg respectively, and the same measurements of eclamptic patients were 136.0 +/- 12.4 mm-Hg and 123.1 +/- 10.6 mm-Hg respectively (p < 0.05, p < 0.05).. Treatment had been found to have negative effects on endothelin-1 levels that is considered to play an important role on etiopathogenesis of eclampsia and preeclampsia.

Topics: Adult; Biomarkers; Blood Pressure; Blood Pressure Determination; Eclampsia; Endothelin-1; Female; Humans; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Third; Probability; Prospective Studies; Risk Assessment; Statistics, Nonparametric; Treatment Outcome

We examined concentrations of endothelin-1 in fetal and maternal plasma samples during hypertensive and normotensive pregnancies. There were significant differences between endothelin-1 levels of eclamptic-preeclamptic mothers' newborns and healthy preterm infants (P < 0.001), but there was no significant difference between endothelin-1 levels of healthy term and preterm infants (P > 0.05).

Topics: Case-Control Studies; Eclampsia; Endothelin-1; Female; Fetal Blood; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pre-Eclampsia; Pregnancy

Endothelin-1 is a potent mitogen and stimulates cell chemokinesis, but these properties have not been investigated in the placenta. Trophoblastic cells from pre-eclamptic pregnancies have a reduced invasive potency and secrete less endothelin-1 than those from normal pregnancies. The present study tested the hypothesis that endothelin-1 affects trophoblast proliferation and invasion.. Trophoblastic cells were isolated from 37 placentae of normal human pregnancies at week 12 by dispastrypsin digestion and subsequently immunopurified to remove nontrophoblastic components. The effects of 5, 10, and 20 nmol/mL endothelin-1 on proliferation and invasion were determined after 24 and 72 hours, respectively, by fluorescence-activated pulse cytometry (FACS) analysis, by measuring DNA synthesis using two different methods and by a Matrigel invasion assay.. All cell preparations uniformly responded to 10 nmol/mL by increased proliferation, owing to a greater proportion of cells in the S-phase of their cell cycle, and invasion. The effects were more pronounced after 24 hours than after 72 hours, by which time cell viability, as measured by the secretion of human chorionic gonadotropin (hCG-beta), had deteriorated. The nonselective receptor antagonist PD 142893 inhibited both endothelin-1 effects.. Endothelin-1 is a mitogenic stimulus for first trimester trophoblastic cells in vitro. The stimulation of cellular invasion represents a novel effect of endothelin-1. We suggest the implication of endothelin-1 in proliferation and invasion of trophoblast and tumour cells and hypothesize a possible role in the etiology of pre-eclampsia.

Topics: Cell Division; Cell Survival; Cells, Cultured; Chorionic Gonadotropin; Eclampsia; Endothelin-1; Female; Humans; Oligopeptides; Pregnancy; Pregnancy Trimester, First; Trophoblasts