dinoprost and Pre-Eclampsia

Overweight is associated with alterations in lipid concentrations and an activation of inflammatory markers and both of these metabolic abnormalities are characteristic of preeclamptic pregnancies before the onset of clinically evident disease. Reactive oxygen species, particularly superoxide anions, evoke endothelial cell activation through many pathways. Markers of lipid peroxidation, including malondialdehyde and 8-epiprostaglandin-F2α, is increased in the plasma of women with preeclampsia, and the low concentrations of water- and lipid-soluble antioxidants in the plasma and the placenta further suggest a state of oxidative stress. This review focuses in the relation between maternal obesity, oxidative stress with development of preeclampsia.

Topics: Antioxidants; Dinoprost; Female; Humans; Inflammation; Lipid Peroxidation; Malondialdehyde; Obesity; Oxidative Stress; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species

The etiology of preeclampsia remains unknown. Because of their widespread and varied effects in the human body, prostaglandins--specifically PGI2, thromboxane A2, PGE, and PGF2 alpha--have come under much investigation as possible etiologic factors. The vasodilating, platelet-disaggregating prostaglandins (PGI2 and PGE) are increased during normal pregnancy and may account for many of the observed hemodynamic changes, which begin as early as the first trimester. In contrast, a relative increase in the vasoconstricting, platelet-aggregating prostaglandins (thromboxane A2 and PGF2 alpha) is seen in preeclampsia. The disruption in the delicate balance between these two opposing pairs of prostaglandins may play an important role in the causation of preeclampsia. The growing body of literature that deals with the relationship between prostaglandins and preeclampsia is discussed.

Topics: Dinoprost; Epoprostenol; Female; Humans; Pre-Eclampsia; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2

After a lag between the recognition of the biologic activity of material derived from seminal vesicles and the actual isolation and identification of prostaglandins, information on the structure, biosynthesis, physiology, and biomedical relevance of this family of substances has expanded explosively in recent years. Their ubiquitous presence in mammalian tissues has contributed to the intense interest in and investigation of their role in normal physiology and a variety of pathologic states. The availability of pure compounds of known chemistry, as well as of numerous agents that interfere with their production or metabolism, continues to allow unravelling of their regulatory influences, mechanism of action, and participation in disease processes. Understanding of the role of prostaglandins in reproductive physiology has led to widespread and effective applications in clinical obstetrics and gynecology, including menstrual disorders, therapeutic abortion, and labor. Their implication in the pathogenesis of toxemia of pregnancy, coupled with expanding information on the general role of prostaglandins in the regulation of hemostasis, has advanced understanding of hemorrhagic and thromboembolic disorders and opened innovative avenues for potential therapeutic intervention.

Topics: Abortion, Induced; Dinoprost; Endometriosis; Female; Humans; Infant, Newborn; Labor, Induced; Labor, Obstetric; Menstruation; Pre-Eclampsia; Pregnancy; Prostaglandins; Prostaglandins F; Reproduction; Uterine Contraction

Our purpose was to determine urinary 9 alpha,11 beta-prostaglandin F2, the primary metabolite of prostaglandin D2, in pregnancies at high risk for hypertensive disorders and the effect of acetylsalicylic acid on 9 alpha,11 beta-prostaglandin F2. Ninety high risk women were randomised to acetylsalicylic acid and placebo groups at 12-14 weeks of gestation, with 43 women in both groups followed up successfully. 9 alpha,11 beta-prostaglandin F2 was determined at baseline, at 24-26, and at 32-34 weeks of gestation. Fifteen normotensive non-pregnant women, 17 normotensive pregnant women at 12-14, and 15 at 30-34 weeks of gestation served as controls. Urinary 9 alpha,11 beta-prostaglandin F2 was significantly higher in pregnant women at 12-14 weeks of gestation as compared to non-pregnant women. High risk pregnancies had higher 9 alpha,11 beta-prostaglandin F2 as compared to normotensive pregnancies at 12-14, and at 30-34 weeks of gestation. Urinary 9 alpha,11 beta-prostaglandin F2 increased throughout pregnancy unrelated to the outcome of the pregnancy or to the treatment.

Topics: Aspirin; Dinoprost; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Time Factors

The vasoactive effect of prostaglandin F(2alpha) (PGF(2alpha)) was studied in in vitro perfused human umbilical arteries following maternal dietary supplementation with omega-3 fatty acids or in pregnancies complicated by a moderate degree of preeclampsia. In most preparations PGF(2alpha) induced a biphasic pressure response with a transient dilatation followed by a constrictory response. The pressure increase was significant in both groups, but no significant differences in the constrictory response or in the proportions of preparations displaying dilatatory responses were observed when compared to appropriate control groups. In conclusion, neither preeclampsia nor dietary supplementation with cod-liver oil had any significant effect on the vasoactive response to PGF(2alpha) in umbilical cord arteries.

Topics: Analysis of Variance; Cod Liver Oil; Corn Oil; Dietary Supplements; Dinoprost; Fatty Acids, Omega-3; Female; Humans; Nutritional Physiological Phenomena; Pre-Eclampsia; Pregnancy; Serotonin; Umbilical Arteries; Vascular Resistance; Vasoconstriction; Vasodilation

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

Topics: Aldosterone; Blood Pressure; Dinoprost; Dinoprostone; Epinephrine; Female; Humans; Norepinephrine; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Prostaglandins E; Prostaglandins F; Renin; Renin-Angiotensin System

MiR-126-3p is a prototype of an endothelial miRNA and has protective effects on endothelial cells. However, little is known about the effects of miR-126-3p on placental trophoblasts. In the present study, we tested the hypothesis that aberrant miR-126-3p expression is present in preeclamptic placenta which contributes to increased inflammatory response in trophoblasts. Placentas were obtained immediately after delivery from normotensive and preeclamptic pregnancies. Villous tissue was either fixed with formalin or used for trophoblast isolation. Trophoblast miR-126-3p expression was assessed by in situ hybridization of formalin-fixed tissue sections and by RT-PCR in cultured syncytiotrophoblasts. Culture medium was collected for measurement of IL-6, TNFα, and 8-Isoprostane production by ELISA and total cellular protein was collected for evaluation of HIF1α expression by Western blot. Effects of overexpression of miR-126-3p in trophoblasts on cytokine production were tested by transfection of pre-mir-126, a precursor of miR-126, into primary isolated trophoblasts. We found that downregulation of miR-126-3p expression was associated with increased IL-6 and TNFα production in trophoblasts from preeclamptic placentas vs. normal placentas. Moreover, transient overexpression of miR-126-3p significantly reduced IL-6 and TNFα production in trophoblasts from both normal and preeclamptic placentas. We further found that increase in miR-126-3p expression not only suppressed hypoxia-induced increases in IL-6 and TNFα production, but also attenuated hypoxia-induced increases in HIF1α expression and 8-Isoprostane production in trophoblasts cultured under hypoxic condition. These results provide plausible evidence that downregulation of miR-126-3p expression reduces anti-inflammatory and anti-oxidative stress activities in placental trophoblasts in preeclampsia.

Topics: Adult; Cell Hypoxia; Cells, Cultured; Dinoprost; Down-Regulation; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; MicroRNAs; Oxidative Stress; Pre-Eclampsia; Pregnancy; Trophoblasts; Tumor Necrosis Factor-alpha; Young Adult

In preeclampsia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preeclampsia. In this in vitro study, term placental explants were used to assess the effects of hydroxychloroquine on placental production of sFlt-1, sEng, TNF-α, activin A, and 8-isoprostane after exposure to hypoxic injury or oxidative stress. Similarly, human umbilical vein endothelial cells (HUVECs) were used to assess the effects of hydroxychloroquine on in vitro markers of endothelial dysfunction. Hydroxychloroquine had no effect on the release of sFlt-1, sEng, TNF-α, activin A, or 8-isoprostane from placental explants exposed to hypoxic injury or oxidative stress. However, hydroxychloroquine mitigated TNF-α-induced HUVEC production of 8-isoprostane and Nicotinanamide adenine dinucleotide phosphate (NADPH) oxidase expression. Hydroxychloroquine also mitigated TNF-α and preeclamptic serum-induced HUVEC monolayer permeability and rescued the loss of zona occludens protein zona occludens 1 (ZO-1). Although hydroxychloroquine had no apparent effects on trophoblast function, it may be a useful endothelial protectant in women presenting with preeclampsia.

Topics: Cell Hypoxia; Cell Survival; Dinoprost; Endoglin; Female; Human Umbilical Vein Endothelial Cells; Humans; Hydroxychloroquine; Inhibin-beta Subunits; Models, Biological; Placenta; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1

To evaluate serum concentration of 8-isoprostane, nitrotyrosine (NT), and total antioxidant capacity (TAC) in pregnant women with diabetes mellitus (DM) considering preconception planning and method of diabetes correction in 11-14 and 30-34 weeks.. The study included 130 women: T1DM (n = 40), T2DM (n = 35), gestational diabetes (GDM, n = 40) and the control group (n = 15). The serum concentrations of NT, 8-isoprostane, and TAC were measured by ELISA methods.. Elevated 8-isoprostane levels were observed in all patients with DM, but this biomarker's maximum values have been seen in T1DM and T2DM on insulin groups. A similar tendency was observed for the concentration of NT in both the 1st and 3rd trimesters. TAC levels showed a statistically relevant decrease in all DM groups compared to the control. The correlation analysis showed a direct correlation between HbA1c and serum 8-isoprostane levels in the 1st (r = .27) and 3rd (r = .3) pregnancy trimesters as well as inverse correlation with TAC level (r = -.48). Direct (NT, 8-isoprostane) and inverse correlations (TAC) were fixated for this biomarker concentration and preeclampsia rates.. DM in pregnancy is related to oxidative stress activation, which might lead to the development of adverse perinatal outcomes.

Topics: Adult; Antioxidants; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dinoprost; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Russia; Tyrosine

Preeclampsia is a prevalent and enigmatic disease, in part characterized by poor remodeling of the spiral arteries. However, preeclampsia does not always clinically present when remodeling has failed to occur. Hypotheses surrounding the "second hit" that is necessary for the clinical presentation of the disease focus on maternal inflammation and oxidative stress. Yet, the studies to date that have investigated these factors have used cross-sectional study designs or small study populations.. In the present study, we sought to explore longitudinal trajectories, beginning early in gestation, of a panel of inflammation and oxidative stress markers in women who went on to have preeclamptic or normotensive pregnancies.. We examined 441 subjects from the ongoing LIFECODES prospective birth cohort, which included 50 mothers who experienced preeclampsia and 391 mothers with normotensive pregnancies. Participants provided urine and plasma samples at 4 time points during gestation (median, 10, 18, 26, and 35 weeks) that were analyzed for a panel of oxidative stress and inflammation markers. Oxidative stress biomarkers included 8-isoprostane and 8-hydroxydeoxyguanosine. Inflammation biomarkers included C-reactive protein, the cytokines interleukin-1β, -6, and -10, and tumor necrosis factor-α. We created Cox proportional hazard models to calculate hazard ratios based on time of preeclampsia diagnosis in association with biomarker concentrations at each of the 4 study visits.. In adjusted models, hazard ratios of preeclampsia were significantly (P<.01) elevated in association with all inflammation biomarkers that were measured at visit 2 (median, 18 weeks; hazard ratios, 1.31-1.83, in association with an interquartile range increase in biomarker). Hazard ratios at this time point were the most elevated for C-reactive protein, for interleukin-1β, -6, and -10, and for the oxidative stress biomarker 8-isoprostane (hazard ratio, 1.68; 95% confidence interval, 1.14-2.48) compared to other time points. Hazard ratios for tumor necrosis factor-α were consistently elevated at all 4 of the study visits (hazard ratios, 1.49-1.63; P<.01). In sensitivity analyses, we observed that these associations were attenuated within groups typically at higher risk of experiencing preeclampsia, which include African American mothers, mothers with higher body mass index at the beginning of gestation, and pregnancies that ended preterm.. This study provides the most robust data to date on repeated measures of inflammation and oxidative stress in preeclamptic compared with normotensive pregnancies. Within these groups, inflammation and oxidative stress biomarkers show different patterns across gestation, beginning as early as 10 weeks. The start of the second trimester appears to be a particularly important time point for the measurement of these biomarkers. Although biomarkers alone do not appear to be useful in the prediction of preeclampsia, these data are useful in understanding the maternal inflammatory profile in pregnancy before the development of the disease and may be used to further develop an understanding of potentially preventative measures.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; C-Reactive Protein; Cohort Studies; Cytokines; Deoxyguanosine; Dinoprost; Female; Humans; Inflammation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Proportional Hazards Models

Preeclampsia is responsible for more than one-third of all maternal deaths in Brazil. The objectives of the present study were to evaluate magnesium status and its association with oxidative stress and inflammation in preeclamptic women, and to identify the predictor variables of the disorder.. The study population consisted of 36 women divided into preeclamptic (n = 18) and control groups (n = 18). The preeclamptic group included women (≥20 weeks of pregnancy) with arterial pressure ≥ 140/90 mmHg and proteinuria >0.3 g/24 h, while the control group comprised pregnant women with no clinical/obstetric complications. Magnesium intake was assessed via a food frequency questionnaire validated for pregnant women in Brazil. Plasma, erythrocyte and urinary magnesium levels were determined by flame atomic absorption spectroscopy, while oxidative stress and inflammatory markers were assessed using standard protocols. Logistic regression analysis was used to identify the predictors of preeclampsia.. Preeclamptic and control groups were similar with respect to magnesium intake and urinary excretion, while plasma and erythrocyte magnesium concentrations were higher in the former group. Plasma magnesium was positively correlated with catalase and glutathione peroxidase activities and with concentrations of interleukin-6 and tumor necrosis factor alpha. Regression analysis showed that plasma magnesium and urinary 8-isoprostane were associated with preeclampsia.. Magnesium status appears to result from homeostatic imbalance and physiological alterations typical of preeclampsia. Increased plasma magnesium and decreased urinary 8-isoprostane were considered predictors of preeclampsia.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Body Weight; Brazil; Case-Control Studies; Catalase; Dinoprost; Female; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Logistic Models; Magnesium; Oxidative Stress; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha; Young Adult

Gestational hypertension (GH) and Preeclampsia, (PE) are the most complicated amongst hypertensive disorders of pregnancy. The mechanism that links hypertension in pregnancy to adverse maternal outcomes is not fully understood though some relate this to endothelial dysfunction originating from an imbalanced angiogenic regulators and oxidative stress biomarkers. This study assessed the correlation between angiogenic regulators and oxidative stress biomarker levels with adverse pregnancy outcomes among GH and PE participants.. A cohort of pregnant women who received antenatal care at the Obstetrics and Gynaecology department of the Komfo Anokye Teaching Hospital (KATH) were followed. During their antenatal visits, 100 developed PE and 70 developed GE, of these, 50 PE and 50 GH gave informed consent. Their blood samples were taken at time of diagnosis and 48 h post-partum. 50 other aged-matched women who did not develop neither GH nor PE were selected as controls. Placental growth factor (PLGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and 8-epi-prostaglandin F2alpha (8-epi-PGF2α) levels were estimated by ELISA and total antioxidant capacity (T-AOC) was measured spectrophotometrically. Graphpad Prism was used for data analysis.. Median levels of sFlt-1, 8-epi-PGF2α and sFlt-1/PLGF were elevated among participants with PE co-existing with intrauterine fetal death (IUFD), placental abruptio, placental previa, HELLP syndrome and intrauterine growth restriction (IUGR) compared to PE without adverse outcomes (p = 0.041, p = 0.005, p = 0.0002). Levels of PLGF, T-AOC and PLGF/sFlt-1 were significantly reduced among participants with PE co-existing with IUFD, placental abruptio, placental previa, HELLP syndrome and IUGR compared to PE without adverse outcomes (p = 0.0013, p = 0.006, p < 0.0001). A significant negative correlation of IUGR (p = 0.0030; p < 0.0001), placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p = 0.0183 and p < 0.000), and postpartum haemorrhage (PPH) (p = 0.0420; p = 0.0044) were associated with both PLGF and T-AOC whilst a significant positive correlation of IUGR, placental abruptio (p < 0.0001; p < 0.0001), IUFD (p < 0.0001; p < 0.0001), stillbirth (p < 0.0001; p < 0.0001), and PPH (p = 0.0043; p = 0.0039) were observed with both sFlt-1 and 8-epi-PGF2α in PE.. Imbalance in the levels of angiogenic regulators and oxidative stress biomarkers correlates with adverse pregnancy outcomes among PE participants. Early identification of these imbalance would alert health care givers in anticipation of adverse pregnancy outcome and thus increased surveillance during pregnancy and parturition and measures to ameliorate the adverse outcome.

Topics: Adult; Angiogenic Proteins; Antioxidants; Biomarkers; Dinoprost; Female; Fetal Growth Retardation; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Oxidative Stress; Placenta; Placenta Growth Factor; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Proteins; Prospective Studies; Vascular Endothelial Growth Factor Receptor-1

Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (P<0.0001), TNF-α (P=0.032) and IFN-γ (P=0.009) at 360 min in maternal venous samples (n=6). There was also a significant increase in ET-1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including malondialdehyde and 8-iso-protaglandin F2α (P=0.009) also show increased levels. Overall, these findings indicate that exposure of ex vivo dually perfused placental tissue to hypoxia provides a useful model for mimicking the inflammatory response characteristic of preeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

Topics: Biomarkers; Cell Hypoxia; Cytokines; Dinoprost; Endothelin-1; Female; Humans; In Vitro Techniques; Kinetics; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Perfusion; Placenta; Pre-Eclampsia; Pregnancy; Up-Regulation

To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications.. A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG).. Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P = .008) and small-for-gestational age infants (P = .002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (<2500 g, P = .043).. Increased maternal oxidative stress at mid-gestation was associated with subsequent pregnancy complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Deoxyguanosine; Dinoprost; Erythrocytes; Female; Gestational Age; Glutathione Peroxidase; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Premature Birth; Prospective Studies; Superoxide Dismutase

The aim of this study is to determine the predictive values of oxidative stress markers and antioxidants in the development of preeclampsia between 10-14 and also at 20-24 weeks of gestation, after the completion of vascular transformation.. Levels of oxidative stress parameters such as malondialdehyde (MDA), lipidhydroperoxide (LHP) and prostaglandin F(2α) (PGF(2α)), oxidized LDL (oxLDL), and antioxidant status parameters such as paraoxonase 1 (PON1), superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels were measured and compared in 21 preeclamptic and 24 healthy pregnant women.. In preeclamptic women, both between 10-14 and also at 20-24 weeks of gestation the levels of oxLDL, MDA and PGF(2α) were significantly higher (P < 0.001, P < 0.001, respectively), PON1, SOD and TAC were significantly lower (P < 0.01, P < 0.001, P < 0.05, respectively) compared to healthy pregnant women; yet there was no significant difference in LHP levels.. Increased levels of serum MDA and PGF(2α), low levels of SOD and PON1 activity, in 10-14 GW may have been associated with preeclampsia etiology. High levels of MDA and PGF(2α) indicate that the oxidative damage is present well before the clinical symptoms occur. A panel of oxidative stress markers such as MDA and PGF(2α) in maternal blood can predict the development of preeclampsia long before clinical onset.

Topics: Adult; Antioxidants; Aryldialkylphosphatase; Biomarkers; Case-Control Studies; Chromatography, High Pressure Liquid; Dinoprost; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Malondialdehyde; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Risk Factors; Superoxide Dismutase

The etiology of preeclampsia (PE) is unknown and the only treatment is removal of the fetus and placenta. The critical changes of this state include the increase of vascular resistance and hypoperfusion in the uteroplacental microcirculation that predispose to hypoxia and ischemia and, therefore, increased oxidative stress through 8-isoprostane, which is characterized by damage to the placenta and endothelium. We undertook this study to compare oxidative stress in pregnant women with PE.. A case-control, cross-sectional and comparative study was undertaken. Pregnant women between 28 and 38 weeks of gestation with and without PE were recruited. Venous blood samples were taken for determination of 8-isoprostane. Obstetrical variables were measured and 8-isoprostane by radioimmunoassay. SPSS v.11 for Windows was used for descriptive statistics. Mean ± standard deviation, correlation and χ(2) were used for comparison between groups.. We studied 45 patients: 20 with PE (44.6%) and 25 without PE (55.4%). The average for 8-isoprostane in preeclamptic patients was 699.2 ± 38.6 pg/dl and without PE was 113.9 ± 52.4 pg/dL (p <0.01), gestational age 32.1 ± 2.6 and 35.1 ± 1.8 weeks, birth weight 1880 ± 238 g and 2787 ± 312 g, respectively. Apgar at birth was similar in both groups.. We found statistical differences in the 8-isoprostane levels in both groups. There was no correlation in perinatal results in both groups according to 8-isoprostane levels. These results could be the basis for the use of antioxidants in the management of PE to counteract tissue damage.

Topics: Adult; Apgar Score; Biomarkers; Birth Weight; Case-Control Studies; Dinoprost; Female; Humans; Infant, Newborn; Oxidative Stress; Pre-Eclampsia; Pregnancy; Statistics, Nonparametric; Young Adult

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.

Topics: Adult; Aldehydes; Amnion; Antigens, CD; Cell Survival; Cells, Cultured; Dinoprost; Endoglin; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Nerve Growth Factors; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Tissue Culture Techniques; Xanthine; Xanthine Oxidase; Young Adult

Maternal periodontal infection is associated with an increased risk for preeclampsia. Periodontal infection is also associated with increased oxidative stress. Our objective was to determine the relationship among maternal periodontal disease, maternal oxidative stress, and the development of preeclampsia.. A secondary analysis of prospectively collected data from the Oral Conditions and Pregnancy Study was performed. A cohort of healthy women enrolled at <26 weeks of gestation underwent an oral examination, serum sampling, and delivery follow-up. A periodontal infection was categorized by clinical parameters as healthy or mild or moderate/severe periodontal infection. Preeclampsia was defined by the American Congress of Obstetricians and Gynecologists criteria as blood pressure >140/90 mmHg and >or=1+ proteinuria on a catheterized specimen. Maternal blood was assayed for 8-isoprostane concentrations using an enzyme-linked immunosorbent assay and stratified as elevated (>or=75th percentile) or not elevated (<75th percentile). Odds ratios (ORs) for preeclampsia were calculated and stratified by periodontal disease and the level of 8-isoprostane concentration.. A total of 34 (4.3%) of 791 women developed preeclampsia. Women with an 8-isoprostane concentration >or=75th percentile at enrollment were more likely to develop preeclampsia compared to women with an 8-isoprostane concentration <75th percentile (38.2% versus 24.4%, respectively; P = 0.07; OR: 1.91; 95% confidence interval [CI]: 0.94 to 3.90). Among women with moderate/severe periodontal disease, an elevated 8-isoprostane concentration (>or=75th percentile) did not significantly increase the likelihood for preeclampsia (adjusted OR: 2.08; 95% CI: 0.65 to 6.60).. Women with oxidative stress early in pregnancy, as measured by an 8-isoprostane concentration >or=75th percentile, were at an increased risk for developing preeclampsia. The presence of periodontal disease did not appear to modify this risk.

Topics: Adult; Biomarkers; Cohort Studies; Dinoprost; Female; Humans; Odds Ratio; Oxidative Stress; Periodontal Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Prospective Studies; Reference Values; Risk Factors; Severity of Illness Index; Statistics, Nonparametric; Young Adult

Preeclampsia is characterized by hypertension and proteinuria developing after 20 weeks of gestation. Increased vasoconstriction can be one of the major underlying pathophysiological event in this syndrome. We examined the role of vasoconstrictor prostanoid, prostaglandin F2α (PGF2α) in preeclamptic and normotensive human umbilical veins.. Umbilical veins were set up in organ bath. The concentration-response curves of PGF2α (endogenous agonist of prostaglandin F receptor) and fluprostenol (prostaglandin F receptor selective agonist) were determined in normal and preeclamptic veins either in the absence or presence of BAY u3405 (thromboxane A2 receptor selective antagonist). PGF2α and its major metabolite concentrations were measured by enzyme immunoassay kit. The expression of vasoconstrictor prostanoid receptors was determined by western blot.. The concentration-dependent contractions to PGF2α and fluprostenol were significantly increased in umbilical vein preparations derived from preeclamptic women compared with those of normotensives. Increased reactivity was related with enhanced sensitivity to these spasmogens in preeclamptic veins. BAY u3405 (10 μmol/l) did not modify the responsiveness to PGF2α in normal umbilical veins whereas moderately reduced the contractions in preeclamptic preparations. Serum concentrations of PGF2α and its major metabolite, 13,14-dihydro-15-keto-PGF2α, were comparable between preeclamptics and normotensives whereas the metabolite concentration was elevated in umbilical cord serum of preeclamptics. 13,14-dihydro-15-keto-PGF2α, release was also increased in umbilical vein preparations of preeclamptic women. An increased prostaglandin F receptor protein expression was determined whereas EP3 and thromboxane A2 protein expressions were unchanged in preeclamptic umbilical veins.. Prostaglandin F and thromboxane A2 receptors activation by PGF2α could be involved in umbilical vasospasm observed in preeclampsia.

Topics: Adult; Blotting, Western; Dinoprost; Female; Humans; Pre-Eclampsia; Pregnancy; Receptors, Thromboxane A2, Prostaglandin H2; Umbilical Veins

Oxidative stress and a generalized inflammatory state are features of preeclampsia (PE). The objective of this study was to compare the levels of products of inflammatory reaction and oxidative stress markers in patients with PE, and to determine the relationship between oxidative stress and inflammation in PE.. Plasma concentrations of high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), and 8-isoprostane were measured in 53 women with PE and 20 age- and BMI-matched normotensive women.. The plasma concentrations of hs-CRP, IL-6, TNF-alpha, and 8-isoprostane were significantly higher in women with PE than in those with normotensive pregnancies, and these parameters, except for 8-isoprostane, were markedly elevated in those with severe PE (SPE), rather than mild PE (MPE). Moreover, plasma levels of 8-isoprostane, not MDA, were significantly correlated with the plasma levels of hs-CRP, IL-6, and TNF-alpha in patients with PE.. These findings suggest that oxidative stress and inflammatory reaction are closely associated with PE, and the interactions between them may participate in the pathogenesis of PE.

Topics: Adult; Biomarkers; C-Reactive Protein; Dinoprost; Female; Humans; Inflammation; Interleukin-6; Malondialdehyde; Oxidative Stress; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha

The aims of this study were to measure the degree of oxidative stress and alterations in plasminogen activator inhibitor (PAI) type 1 and PAI-2 ratio in women with early-onset and late-onset preeclampsia.. A case-control study was conducted in women with early-onset (24-32 weeks' gestation; n=18) and late-onset (35-42 weeks' gestation; n=20) preeclampsia and in control pregnant women at corresponding gestational weeks. Placenta, urine, and serum samples were collected.. In early-onset preeclampsia, the median placental concentration of 8-iso-prostaglandin (PG)-F2alpha was higher and the PAI-1 to PAI-2 ratio higher than in early controls. These values did not differ between women with late-onset preeclampsia and their corresponding controls. Serum concentrations of 8-iso-PGF2alpha and vitamins C and E did not differ between cases and controls.. Early-onset but not late-onset preeclampsia is associated with increased placental oxidative stress and increased PAI-1 to PAI-2 ratio.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Dinoprost; Female; Humans; Oxidative Stress; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pre-Eclampsia; Pregnancy; Vitamin E

To compare oxidative stress in patients with preeclampsia (PE) or intrauterine growth restriction (IUGR) vs. normal pregnancy (controls) during 48 h after delivery.. Women with singleton pregnancies were recruited immediately after delivery (gestational age >26.0 weeks). Women with PE or IUGR were matched with healthy controls by age, BMI, gestational age and delivery mode. Venous blood samples and urine samples were tested for oxidative stress products 24 h and 48 h after delivery.. Plasma malondialdehyde (MDA) concentration 24 h after delivery was significantly higher in subjects with PE or IUGR (3.41+/-1.14 micromol/L, n=20) than in controls (2.91+/-0.82 micromol/L, n=38) (P=0.04). Urine iPF(2alpha)-VI declined from 24 to 48 h after delivery significantly in controls (P=0.006) and not in subjects with PE or IUGR (P=0.71).. Of the markers tested only MDA is indicating higher oxidative stress in women with PE/IUGR than in normal pregnancy and only at 24 h after delivery. No consistent pattern of change in the oxidative stress markers exists between 24-48 h after delivery.

Topics: Adult; Dinoprost; Female; Fetal Growth Retardation; Humans; Malondialdehyde; Oxidative Stress; Pre-Eclampsia; Pregnancy; Statistics, Nonparametric

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Biomarkers; Birth Weight; Congenital Abnormalities; Deoxyguanosine; Dinoprost; DNA Damage; Female; Gestational Age; Humans; Infant, Newborn; Lipid Peroxidation; Male; Middle Aged; Oxidants; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Young Adult

Preeclampsia (PE) and diabetes mellitus (DM) are associated with oxidative stress. DM is complicated with formation of advanced glycation end products (AGEs), which are associated with oxidative stress. We hypothesized that elevated serum AGE would be found in pregnancies complicated by PE or DM.. Circulating AGEs, 8-isoprostane, vitamin E, and antioxidant capacity were analyzed from study patients.. Serum AGE was elevated both in patients with type 1 DM and gestational DM, but not in PE, compared with controls. 8-isoprostane was elevated in patients with type 1 DM and PE compared with controls.. AGEs and 8-isoprostane are not elevated in parallel in pregnancies complicated with PE or DM, suggesting biological heterogeneity.

Topics: Adult; Biomarkers; Case-Control Studies; Diabetes, Gestational; Dinoprost; Female; Ferric Compounds; Glycation End Products, Advanced; Humans; Lysine; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Vitamin E; Young Adult

Preeclampsia is characterized by intense and prolonged vasoconstriction. Rho A-mediated calcium sensitization is central to prolonged contractility of vascular smooth muscle. The aims of this study are (1) to investigate mRNA expression levels of Rho A/Rho kinases in placental tissues from normotensive and preeclamptic women and (2) to investigate the effects of 2 isoprostanes, 8-iso prostaglandin F(2)( alpha) (8-iso PGF(2 alpha) ) and 8-iso prostaglandin E(2) (8-iso PGE(2)), on small placental and myometrial vessel resistance and to determine if their effects were mediated via the Rho kinase pathway. Real-time reverse transcription polymerase chain reaction for Rho A, ROCK I, and ROCK II was performed on total RNA from normotensive and preeclamptic placentae. The effects of 8- iso PGF(2 alpha) and 8-iso PGE(2) (alone and with the specific Rho kinase inhibitor Y-27632) on placental and myometrial vessels (<400 microm) were measured and compared with control recordings. Rho A mRNA expression levels were significantly higher in placentae from preeclamptic women than in placentae from normotensive women (P < .01). There was no significant difference in expression levels of ROCK I and ROCK II between both tissue types (P > .05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect on both vessel types (P < .001). This effect was antagonized by Y-27632 in placental arteries but not in myometrial arteries. Increased Rho A mRNA expression in placentae from preeclamptic women is suggestive of a role for the Rho kinase pathway in the modulation of the placental vasculature in this condition. Isoprostanes exert their vasocontractile effect, in placental vasculature, in part via the Rho kinase pathway.

Topics: Dinoprost; Dinoprostone; Female; Humans; Isoprostanes; Myometrium; Placenta; Pre-Eclampsia; Pregnancy; rho-Associated Kinases; RNA, Messenger; Signal Transduction; Vasoconstriction

The onset of preeclampsia is associated with increased maternal insult that could affect placental function. By increasing sodium intake (0.9% or 1.8% NaCl in drinking water) during the last week of gestation in the rat, we developed an animal model that shows many characteristics of preeclampsia such as increased blood pressure, decreased circulatory volume and diminished activity of the renin-angiotensin-aldosterone system. The aim of the present study was to determine in this model whether maternal perturbations in pregnancy lead to placental oxidative stress. Sprague-Dawley pregnant rats receiving salted-water were compared to not-supplemented pregnant rats. Markers of oxidative stress, ensuing cell death, and changes in the production of vasoactive substances (prostanoids: thromboxane, TxB(2); and prostacyclin, PGF(1alpha)) and the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in the placenta. In tissue from pregnant rats on 1.8% NaCl supplement, 8-iso-PGF(2alpha) levels, TxB(2)/6-keto-PGF(1alpha) ratios, total TNF-alpha RNA expression, as well as the apoptotic index (Bax/Bcl-2 ratio) and endothelial nitric oxide synthase protein expression increase while total glutathione content decreases. These findings demonstrate that maternal insult during gestation induced an imbalance in the oxidative environment in the placenta favouring oxidation. This was accompanied by an increased synthesis of vasoconstrictive substances and TNF-alpha by the placenta as well as the increased rate of placental cell apoptosis.

Topics: Animals; Apoptosis; Dinoprost; Disease Models, Animal; Female; Gene Expression; Glutathione; Nitric Oxide Synthase Type III; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Prostaglandins; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Pre eclampsia represents a state of increased or prolonged vasoconstriction, partially linked to the potent vasocontractile effect of isoprostanes. The process of Rho A-mediated calcium sensitisation is inherent to a state of prolonged contractility in many smooth muscle types. The aim of this study was (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and II) in the umbilical artery from normotensive and pre eclamptic women and (2) to determine whether the effects of two isoprostanes, 8-iso prostaglandin F(2alpha) (8-iso PGF2alpha) and 8-iso prostaglandin E(2) (8-iso PGE(2)), on umbilical artery tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using primers for Rho A, ROCK I and ROCK II was performed on total RNA isolated from umbilical artery specimens obtained from normotensive and pre eclamptic women. The effects of both isoprostanes (n = 6) (in the absence and presence of the specific Rho kinase inhibitor Y-27632), on umbilical artery tone were measured, and compared with control recordings. Rho A mRNA expression levels were significantly lower in umbilical artery samples obtained from pre eclamptic women (n = 4) in comparison to those from normotensive women (n = 6) (P < 0.05). ROCK I and ROCK II mRNA levels were similar in both vessel types (P > 0.05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect (n = 7) (P < 0.001) on umbilical artery. For 8-iso PGE(2), this effect was antagonised by Y-27632 (n = 6) (P < 0.01). The significant reduction of Rho A mRNA levels in umbilical arteries from pregnancies complicated by pre eclampsia may serve to counteract the diminished perfusion associated with the pathophysiology of pre eclampsia. The vasocontractile effect of 8-iso PGE(2) in pre eclampsia may in part be mediated via the Rho kinase pathway.

Topics: Acute-Phase Proteins; Amides; Analysis of Variance; Case-Control Studies; Dinoprost; Dinoprostone; Female; Humans; Intracellular Signaling Peptides and Proteins; Isoprostanes; Muscle, Smooth, Vascular; Pre-Eclampsia; Pregnancy; Protein Isoforms; Protein Serine-Threonine Kinases; Pyridines; Reverse Transcriptase Polymerase Chain Reaction; rho-Associated Kinases; RNA, Messenger; Tissue Culture Techniques; Umbilical Arteries; Vasoconstrictor Agents

To explore the relationship between the levels of maternal oxidative stress and glycaemia during pregnancy and to compare the predictive values of 8-epimer of prostaglandin F(2alpha) (8-isoPGF(2alpha)) and mean arterial pressure (MAP) in midpregnancy for the development of hypertensive complications in later pregnancy.. Prospective observational study as an ancillary study to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study.. Obstetric clinics and wards of a university teaching hospital in Hong Kong.. Selected women with singleton pregnancies attending the antenatal clinic.. Pregnant women who met HAPO inclusion criteria were recruited for the study. Glucose tolerance was assessed by a 75-g 2-hour oral glucose tolerance test (OGTT) at 24-32 weeks of gestation. Fasting plasma samples for 8-isoPGF(2alpha) estimation and urine samples for 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) assays were collected and blood pressures measured during the OGTT visit. Random plasma and urine samples were also obtained at 34-37 weeks. Glucose results were unblinded to the attending obstetrician if limits preset under the HAPO protocol were met.. Maternal plasma 8-isoPGF(2alpha) and urinary 8-isoPGF(2alpha) and 2,3-dinor 8-isoPGF(2alpha) both at the time of OGTT (24-32 weeks) and at 34-37 weeks of gestation. Incidence of pre-eclampsia and gestational hypertension.. Of the 408 women who attended for OGTT at 24-32 weeks, two met the glucose criteria for unblinding and 25 had missing 8-isoPGF(2alpha) values and thus were excluded from analysis. Of the 381 women, 338 (88.7%) attended for random plasma samples at 34-37 weeks. Significant correlations were observed between maternal fasting plasma isoprostane and both fasting (r= 0.20; P < 0.001) and 2-hour (r= 0.39; P < 0.001) plasma glucose levels at the time of OGTT. Gestational hypertension/pre-eclampsia occurred in 17 (4.2%) women, and at the time of OGTT, they had significantly higher fasting plasma 8-isoPGF(2alpha) (P < 0.001), urine 8-isoPGF(2alpha) (P < 0.005) and urine 2,3-dinor 8-isoPGF(2alpha) to creatinine ratios (P < 0.001), as well as higher MAP (P < 0.001) than women who remained normotensive. At 34-37 weeks, only random plasma 8-isoPGF(2alpha) was significantly higher (P < 0.001) among the women with gestational hypertension/pre-eclampsia.. Plasma markers of oxidative stress were positively correlated with plasma glucose at the time of OGTT (24-32 weeks). Women who subsequently developed gestational hypertension/pre-eclampsia had significantly higher plasma and urine markers of oxidative stress at the time of OGTT but only higher plasma markers at 34-37 weeks. Plasma 8-isoPGF(2alpha) appears to be a very good predictor of subsequent gestational hypertension/pre-eclampsia when measured at the time of OGTT, but its ability to discriminate deteriorates as pregnancy advances.

Topics: Adult; Blood Glucose; Dinoprost; Female; Glucose Tolerance Test; Humans; Hypertension, Pregnancy-Induced; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Prospective Studies

Preeclampsia is associated with oxidative stress in maternal circulation. The purpose of this study was to explore oxidative stress and antioxidants in the fetal circulation in preeclampsia. Women with preeclampsia (n = 19) or uncomplicated pregnancies (n = 33) delivered by cesarean section were included. Blood was sampled separately from the umbilical vein and artery. 8-Iso-prostaglandin F(2alpha) (8-isoprostane), a stable product of lipid peroxidation, is a reliable marker of oxidative stress. Concentration of total 8-isoprostane in cord plasma was analyzed by gas chromatography-mass spectrometry. Antioxidant status was evaluated measuring ferric reducing ability of plasma and vitamin E. There was no difference between preeclampsia and control groups regarding median plasma concentration of 8-isoprostane in umbilical vein (955 versus 780 pg/mL, p = 0.41) or in umbilical artery (233 versus 276 pg/mL, p = 0.65). Concentration of 8-isoprostane was much higher in plasma from the umbilical vein than artery, suggesting placenta as the source of 8-isoprostane. Median ferric reducing ability of plasma concentration was higher in preeclampsia than in controls, both in the umbilical vein and artery. Median vitamin E concentration in the umbilical vein was higher in preeclampsia, but no difference was found in the umbilical artery. In conclusion, no evidence of increased oxidative stress, evaluated by 8-isoprostane concentration, was found in fetal circulation in preeclampsia.

Topics: Adult; Antioxidants; Biomarkers; Dinoprost; F2-Isoprostanes; Female; Fetal Blood; Fetus; Humans; Maternal-Fetal Exchange; Oxidative Stress; Pre-Eclampsia; Pregnancy; Umbilical Arteries; Umbilical Veins; Vitamin E

We investigated the role of microparticles in vascular dysfunction of the multisystemic disorder of preeclampsia in women's omental arteries or mouse arteries. Preeclamptic women displayed increased circulating levels of leukocyte- and platelet-derived microparticles compared with healthy pregnant individuals. Microparticles from preeclamptic, but not healthy, pregnant women induced ex vivo vascular hyporeactivity to serotonin in human omental arteries and mouse aortas. Hyporeactivity was reversed by a nitric-oxide (NO) synthase inhibitor and associated with increased NO production. In the presence of a cyclooxygenase (COX)-2 inhibitor, serotonin-mediated contraction was partially reduced in arteries treated with healthy microparticles but was abolished after treatment with preeclamptic microparticles. This was associated with increased 8-isoprostane production. Preeclamptic microparticles induced up-regulation of inducible nitric-oxide synthase and COX-2 expression, evoked nuclear factor-kappaB activation, and enhanced oxidative and nitrosative stress. Interestingly, the microparticles originating most probably from leukocytes were responsible for the COX-2 vasoconstrictor component of preeclamptic microparticles, whereas those of platelet origin were mainly involved in NO release. Moreover, vascular hyporeactivity was observed in arteries taken from mice treated in vivo with preeclamptic microparticles. This study demonstrates pathophysiological relevance and provides a paradoxical effect of preeclamptic microparticles associated with proinflammatory properties on vessels, leading to enhanced NO and superoxide anion levels and counteraction of increased COX-2 metabolites.

Topics: Animals; Aorta; Arteries; Cell Membrane; Cyclooxygenase 2 Inhibitors; Dinoprost; Endothelium, Vascular; Female; Humans; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Pre-Eclampsia; Pregnancy; Prostaglandins; Serotonin; Transcription Factor RelA; Vasculitis; Vasoconstriction

A current theory holds that oxidative stress, ie, an imbalance between maternal prooxidants and antioxidants, is a component of preeclampsia. It is uncertain whether such an imbalance occurs before clinical recognition of the syndrome or whether it is related to diet.. We measured urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha), which is an indicator of oxidative damage to lipids, and the total antioxidant power, which is a global measure of antioxidant status, at the entry to prenatal care. We also examined the relation of these indexes to diet during pregnancy.. A cohort of 307 gravidae from Camden, NJ, was studied from entry to prenatal care (at 15.0 +/- 0.49 wk gestation). Measures of the maternal diet were obtained by 24-h recall.. Risk of preeclampsia was increased 5-fold with higher urinary isoprostane excretion and decreased 3-fold with higher total antioxidant power. Over the course of pregnancy, there were significant trends for an association of higher isoprostane excretion with increased consumption of energy-adjusted fat, polyunsaturated fat, and polyunsaturated fatty acids (n-3, n-6, and linoleic and linolenic fatty acids), whereas total antioxidant power was not related to diet.. Increased urinary excretion of isoprostane and decreased antioxidant production is an imbalance that is consistent with oxidative stress, and it precedes clinical recognition of preeclampsia. The maternal diet is an underlying factor that provides an environment for free radical generation.

Topics: Adolescent; Adult; Age Factors; Antioxidants; Biomarkers; Cohort Studies; Diet; Dinoprost; Female; Humans; Linear Models; Lipid Metabolism; Lipid Peroxidation; Maternal Nutritional Physiological Phenomena; Mental Recall; Oxidative Stress; Pre-Eclampsia; Pregnancy; Prospective Studies

We studied fetal endothelial function in a model of preeclampsia induced by Nomega-nitro-l-arginine methylester (L-NAME) administration in pregnant rats.. Aortic segments from term fetuses and 2-day-old Wistar rats treated with L-NAME (0.5 mg/mL in drinking water) (fetuses from hypertensive rats, FH, and newborns from hypertensive rats, NH) and from untreated rats (fetuses from normotensive rats, FN, and newborns from normotensive rats, NN) were obtained. Endothelium-dependent and -independent relaxations were determined by the response to 1 microM acetylcholine (ACh) and 1 microM sodium nitroprusside (SNP), respectively, after precontraction with 3 microM prostaglandin F2alpha. The role of nitric oxide in ACh relaxation was assessed by incubation with 0.1 mM N(G)-monomethyl-l-arginine (L-NMMA) or 0.1 mM l-arginine (l-Arg). Precontraction with 50 mM potassium chloride assessed the role of hyperpolarizing mechanisms.. In FH, ACh-induced relaxation was reduced (FH 34.2 +/- 4%, FN 45.8 +/- 2%, P < .05), whereas that of SNP was enhanced (FH 68.4 +/- 5%, FN 50.4 +/- 4%, P < .05). l-Arg did not reverse the impairment of ACh relaxation. L-NMMA reduced ACh relaxation in FN but increased it in FH; this increase was abolished by potassium chloride precontraction and by 1 microM capsaicine, a calcitonin-gene related peptide inhibitor. The hyperpolarizing component of ACh relaxation was reduced in FH as compared with FN. By contrast, ACh relaxation was greater in NH than in NN, with the relative participation of nitric oxide and hyperpolarizing-related components being similar in both groups.. Fetal ACh relaxation was impaired in this preeclampsia-like model. This impairment is probably not exclusively an effect of L-NAME but could reflect endothelial dysfunction that disappears after birth.

Topics: Acetylcholine; Animals; Arginine; Dinoprost; Disease Models, Animal; Enzyme Inhibitors; Female; Fetus; Muscle Contraction; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroprusside; omega-N-Methylarginine; Potassium Chloride; Pre-Eclampsia; Pregnancy; Rats; Rats, Wistar; Vasodilation

This study is designed to evaluate whether oxidative stress and inflammation are involved in severe pre-eclampsia compared to normal pregnancy and non-pregnancy. We have measured plasma and urinary levels of 8-iso-PGF2alpha, a major isoprostane as an indicator of oxidative stress; plasma and urinary 15-keto-dihydro-PGF2alpha, a major metabolite of cyclooxygenase-catalysed PGF2alpha as an indicator of inflammatory response, and plasma -alpha-and -gamma-tocopherol in 18 pre-eclamptic, 19 normal pregnancy and 20 non-pregnant women. Pregnant women had significantly higher levels of 8-iso-PGF2alpha and PGF2alpha metabolite as compared to the non-pregnancy. Levels of 8-iso-PGF2alpha in the pre-eclamptic women did not differ from the normal pregnancy but PGF2alpha metabolite levels were significantly higher in normal pregnancy. On the other hand, gamma-tocopherol levels were significantly lower in pre-eclampsia than normal pregnancy. In contrast, the concentration of alpha-tocopherol was very similar between the groups. alpha-and gamma-tocopherol levels were significantly lower in pregnancy compared to non-pregnancy. Although no direct evidence of oxidative stress and inflammatory response was observed in severe pre-eclampsia, a reduction of gamma-tocopherol suggests the possible precedence of oxidative stress in this condition. Higher levels of isoprostanes and prostaglandin metabolite in late pregnancy suggest the importance of both free radicals and cyclooxygenase-catalysed oxidation products in normal biological processes of pregnancy.

Topics: Adult; alpha-Tocopherol; Antioxidants; Biomarkers; Dinoprost; Female; gamma-Tocopherol; Humans; Inflammation; Lipid Peroxidation; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Sweden

The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preeclampsia in the blood of pregnant women in whom preeclampsia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preeclampsia and with women who were at low risk for the development of preeclampsia.. This was a prospective case control study. The subjects were women at risk of preeclampsia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preeclampsia developed later, in 17 women without preeclampsia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preeclampsia.. Ascorbic acid was reduced early in preeclampsia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preeclampsia.. Gestational profiles of several markers were abnormal in the group with preeclampsia, and some of the markers that may prove useful in the selective prediction of preeclampsia were identified.

Topics: Algorithms; Blood Pressure; Case-Control Studies; Dinoprost; Endothelium; F2-Isoprostanes; Female; Humans; Infant, Newborn; Infant, Small for Gestational Age; Lipids; Longitudinal Studies; Oxidative Stress; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pre-Eclampsia; Pregnancy; Risk Factors; ROC Curve; Sensitivity and Specificity

Lectinlike oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL (ox-LDL), is proposed to be involved in endothelial dysfunction and in the pathogenesis of atherosclerosis. Preeclampsia is a pregnancy complication diagnosed by hypertension and proteinuria, characterized by endothelial dysfunction, and supposedly caused by compounds from hypoxic uteroplacental tissues. A feature of preeclampsia is formation of foam cells in maternal arterial walls of gestational tissue ("acute atherosis"). Oxidative stress is believed to play a role in the pathophysiology of preeclampsia. 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo, is biologically active in vitro, and is elevated in preeclamptic plasma and gestational tissue. In the present article, we hypothesized that 8-iso-PGF(2alpha) could induce the expression of LOX-1 in trophoblastic cells (JAR). We demonstrated augmented cellular uptake of (125)I-tyraminylcellobiose ox-LDL in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) versus control cells. Ligand blots revealed an increased binding of ox-LDL to LOX-1 in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L). Incubation with 8-iso-PGF(2alpha) (10 micromol/L) also resulted in augmented LOX-1 protein levels (Western blots) and mRNA levels (Northern blots). JAR cells transfected with 3 copies of a nuclear factor-kappaB binding site demonstrated dose-dependent activation of the reporter gene luciferase after incubation with 8-iso-PGF(2alpha) (0 to 10 micromol/L). We also demonstrated increased accumulation of neutral fats in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) and ox-LDL compared with controls by oil red O staining. We speculate a potential role of isoprostanes and LOX-1 in preeclampsia in the development of "acute atherosis" of gestational spiral arteries.

Topics: Azo Compounds; Blotting, Northern; Blotting, Western; Cell Line; Coloring Agents; Dinoprost; F2-Isoprostanes; Female; Humans; Oxidative Stress; Pre-Eclampsia; Pregnancy; Receptors, LDL; Receptors, Oxidized LDL; RNA, Messenger; Scavenger Receptors, Class E; Transfection

The effects of 8-epi-prostaglandin F(2alpha)(8-epi-PGF(2alpha)) and the thromboxane A(2)-mimetic U46619 were examined on isolated human fetal placental arteries obtained from normal pregnancies and from those complicated by pre-eclampsia. The effects of these agents were examined on both conduit and resistance arteries. 8-epi-PGF(2alpha)was found to be markedly less potent than U46619 in constricting both size vessels. Vasoconstrictor EC(50)s for 8-epi PGF(2alpha)were 4.10x10(-7) m (2.02-8.35x10(-7) m) (mean, 95 per cent CI and 2.05x10(-6) m (0.43-9.89 x10(-6) m) in conduit and resistance arteries, respectively. The maximum vasoconstriction produced by 8-epi-PGF(2alpha)(112+/-17 per cent), (relative to maximum KCl induced vasoconstriction) in conduit vessels was significantly less than that caused by U46619 (152+/-20 per cent). In resistance vessels the maximum vasoconstrictor effects to 8-epi-PGF(2alpha)(208+/-10 per cent) and U46619 (201+/-19 per cent) were similar, and in both cases significantly greater than the maximal effects seen in conduit vessels. U46619 displayed a similar vasoconstrictor potency in both conduit (EC(50)=1.21x10(-9) m, 0.58-2.51x10(-9) m) and resistance arteries [EC(50)=5.95x10(-9) m, (0.81-43.60x10(-9) m] as was found for 8-epi PGF(2alpha). 8-epi-PGF(2alpha)was equipotent in resistance arteries obtained from women with severely pre-eclamptic pregnancies (EC(50)=1.25x10(-6) m, 0.25-6.17x10(-6) m) compared with normotensive controls. However, the maximum vasoconstrictor effect induced by 8-epi-PGF(2alpha)in placental resistance arteries was significantly reduced (99+/-20 per cent) in vessels obtained from severely pre-eclamptic compared with normal pregnancies. These results indicate that 8-epi-PGF(2alpha)displays differential vasoconstrictor activity in the fetal-placental vasculature. Furthermore the vasoconstrictor effects of 8-epi-PGF(2alpha)are reduced in pre-eclampsia, the effect being selective to placental resistance vessels. This reduction may occur as a result of more serious disturbances in the placental microcirculation with the disease process in pre-eclampsia.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adolescent; Adult; Arteries; Dinoprost; Female; Humans; Male; Placenta; Potassium Chloride; Pre-Eclampsia; Pregnancy; Receptors, Thromboxane; Vascular Resistance; Vasoconstrictor Agents

This study was undertaken to address the role of oxidative stress in preeclampsia.. We measured urinary 8,12-iso-iPF(2alpha)-VI, a chemically stable, free-radical catalyzed product, in a case control study of severe preeclampsia nested within the trial of Calcium for Preeclampsia Prevention. Cases included 29 women who developed severe preeclampsia and from whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia, 3 to 9 weeks before, and 1 day before through delivery. Controls did not develop hypertension or proteinuria and were matched to cases by center, gestational age at each of 3 corresponding urine collections, and date of enrollment.. Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and controls before or at diagnosis of preeclampsia, nor did it vary with gestational age.. These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia.

Topics: Adult; Case-Control Studies; Dinoprost; Female; Gestational Age; Humans; Lipid Peroxides; Pre-Eclampsia; Pregnancy; Reference Values; Severity of Illness Index

Neutrophil activation occurs in women with preeclampsia and is resolved after delivery. The present study examined whether circulating factors in plasma of women with preeclampsia caused neutrophil activation and lipid peroxidation. Twenty-one women with proteinuric preeclampsia were matched for age and gestational age with 19 normal pregnant women. Plasma was collected from all subjects before delivery and at 6 weeks postpartum and incubated with autologous white-cell buffy coat collected at the postpartum visit. Neutrophil activation was assessed by level of CD11b and CD18 expression after incubation with autologous antepartum or postpartum plasma. Lipid peroxidation was assessed by measurement of F(2)-isoprostanes in plasma, plasma-white cell incubates, and urine. Neutrophil CD11b and CD18 expression was not differentially altered by incubation with plasma from either women with preeclampsia or normal pregnant women and was similar between groups when incubation was performed with plasma collected after delivery. In preeclampsia, plasma F(2)-isoprostanes were significantly increased before and after delivery compared with controls. Plasma F(2)-isoprostanes were increased 2-fold after incubation of plasma with buffy coat, but preeclamptic women had higher levels compared with those of controls when either pregnant or postpartum plasma was used. In pregnant preeclamptics, plasma F(2)-isoprostanes were positively correlated with lymphocyte count. Six weeks after delivery, plasma F(2)-isoprostanes in the preeclamptic women were significantly positively associated with lymphocyte count and cholesterol and negatively associated with albumin. In conclusion, the present study does not suggest that a stable circulating factor causes neutrophil activation in preeclampsia. However, lipid peroxidation is elevated before and after delivery in women with preeclampsia, which suggests that these women may have an underlying predisposition to increased oxidative stress that may be driven by or contribute to a persistent low-grade inflammatory response.

Topics: Adult; CD18 Antigens; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Macrophage-1 Antigen; Neutrophil Activation; Neutrophils; Postpartum Period; Pre-Eclampsia; Pregnancy

We determined placental tissue levels, production rates, and secretion rates of isoprostanes for placentas obtained from women with normal pregnancies and women with preeclampsia, a hypertensive disorder of pregnancy. Isoprostanes are markers of oxidative stress that exert biological actions such as vasoconstriction. Placental tissue was rinsed and immediately frozen in liquid nitrogen to determine tissue levels of total and free isoprostane. Placental tissue pieces were also incubated in serum-free DMEM for 48 h at 37 degrees C in 95% air/5% CO(2) to determine production rates. Isolated placental cotyledons were perfused for the determination of secretion rates. All samples were analyzed by EIA for isoprostane using an antibody specific for 8-Iso-PGF(2) (15-F(2t)-IsoP). In addition, medium samples were analyzed for malondialdehyde (MDA), a breakdown product of lipid peroxidation. We found that tissue levels of free isoprostane and total isoprostane (free plus esterified forms) were significantly higher for preeclamptic placentas than for normal placentas. Concentrations of isoprostane and MDA in the medium increased progressively during 48 h of incubation of placental explants. At 48 h of incubation, the mean concentrations of both isoprostane and MDA were significantly higher for the placentas from preeclamptic women than for the placentas from normal pregnant women. Concentrations of MDA were highly correlated with those of isoprostane. Induction of oxidative stress with xanthine plus xanthine oxidase increased placental production of isoprostane by normal tissue to a level similar to that of preeclamptic tissue. Placental secretion of isoprostane was eightfold greater toward the maternal side of the placenta than toward the fetal side, and was increased sixfold on the maternal side and twofold on the fetal side by inducing oxidative stress with t-butyl hydroperoxide. This study presents new information that isoprostanes are formed and secreted by the human placenta and provides convincing evidence that oxidative stress and lipid peroxidation are abnormally increased in placentas of preeclamptic women.

Topics: Adult; Case-Control Studies; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Vasoconstrictor Agents

Our purpose was to measure and compare plasma, urinary, and salivary concentrations of 8-epi-prostaglandin F(2alpha) (8-isoprostane) in women with normotensive pregnancies and the respective concentrations in pregnancies complicated by preeclampsia.. Plasma, urinary, and salivary 8-isoprostane levels were measured in pregnant women with preeclampsia (n = 40), normotensive pregnant women (n = 20), and nonpregnant women (n = 10). One-way analysis of variance was used to determine significant differences.. Plasma free 8-isoprostane concentrations were increased in women with severe preeclampsia (342 +/- 50 pg/mL), in comparison with nonpregnant women (129 +/- 17 pg/mL) and normotensive pregnant women (150 +/- 11 pg/mL; P =.003, and.0001, respectively). Urinary excretion of 8-isoprostane was slightly but not significantly decreased in preeclampsia (1200 +/- 227 pg/mL), in comparison with urinary excretion in nonpregnant women (1625 +/- 364 pg/mL) and normotensive pregnant women (2149 +/- 432 pg/mL). Salivary concentrations of 8-isoprostane were increased in normotensive women (496 +/- 113 pg/mL), in comparison with nonpregnant women (150 +/- 27 pg/mL) but were not related to preeclampsia (419 +/- 96 pg/mL; P

Topics: Blood Pressure; Dinoprost; F2-Isoprostanes; Female; Humans; Pre-Eclampsia; Pregnancy; Reference Values; Saliva

The prostaglandin-like compound 8-iso-prostaglandin F(2alpha) represents an index of oxidative stress and has the ability to induce endothelial derangement, platelet activation, and vasoconstriction. In women with preeclampsia the decidual spiral arteries contain lipid deposits (acute atherosis). Analogously to the elevated level of 8-iso-prostaglandin F(2alpha) demonstrated in atherosclerotic lesions, we hypothesized that 8-iso-prostaglandin F(2alpha) level would be elevated in preeclamptic decidua basalis tissues.. Decidua basalis tissues were obtained by vacuum aspiration and placental tissues were obtained by excision at cesarean delivery from 16 preeclamptic and 15 normal pregnancies. Total and free 8-iso-prostaglandin F(2alpha) concentrations were quantified with an enzyme immunoassay technique after lipid extraction and separation.. The content of free 8-iso-prostaglandin F(2alpha) in preeclamptic decidual tissues was found to be significantly elevated with respect to that in control tissues. The content of total 8-iso-prostaglandin F(2alpha) did not differ significantly between the groups in either placenta or decidua basalis.. We propose that free 8-iso-prostaglandin F(2alpha) released from the decidua basalis in preeclampsia may mediate maternal vascular dysfunction and platelet activation.

Topics: Adult; Birth Weight; Blood Pressure; Body Mass Index; Decidua; Dinoprost; F2-Isoprostanes; Female; Humans; Infant, Newborn; Parity; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Time Factors

The objective of this study was to clarify the role of the main proinflammatory cytokines (interleukin [IL]-1, IL-6, tumor necrosis factor [TNF]-alpha) in the pathogenesis of preeclampsia and how these cytokines affect one another and the production of prostaglandins (PGs).. The concentrations of cytokines and PGs in supernatants of placental tissue from preeclamptic and normal women were determined by enzyme-linked immunosorbent assay.. The concentrations of the PGs from unstimulated preeclamptic placental tissue were significantly higher compared to the concentrations of PGs from normal unstimulated placental tissue. Significant levels of IL-1beta were observed only in the supernatants of preeclamptic placental tissue. Of interest, an increase in TNF-alpha production was detected in the supernatants of IL-1-stimulated preeclamptic placental tissue.. The overproduction of TNF-alpha may be related not only to the effect of a stimulant like IL-1beta, but mainly to the lack of mechanisms down-regulating the production of TNF-alpha.

Topics: Dinoprost; Dinoprostone; Female; Humans; Interleukin-1; Interleukin-6; Placenta; Pre-Eclampsia; Pregnancy; Tumor Necrosis Factor-alpha

Eicosanoids play an important role in the pathogenesis of preeclampsia. The major eicosanoid metabolite reported to be secreted by endothelial cells, the vasodilator prostacyclin, is generally reduced in preeclampsia. By contrast, it was shown previously that prostacyclin secretion by cultured human umbilical vein endothelial (HUVE) cells is increased significantly after exposure to blood from preeclamptic women. In the current study, eicosanoid profiles in conditioned media from HUVE cells incubated with pregnancy plasma were analyzed by high-performance liquid chromatography, thin layer chromatography and quantitative radio- and enzyme immunoassays. More prostaglandin F2alpha, prostacyclin and 8-isoprostane were secreted after exposure to plasma from preeclamptic women than plasma from matched, normal pregnant patients. Predominant secretion of the vasoconstrictor prostaglandin F2alpha by HUVE cell cultures and a stimulatory effect of preeclampsia plasma on eicosanoid biosynthesis underscore the importance of bioactive lipids in the vasospasm associated with clinical preeclampsia.

Topics: Adult; Analysis of Variance; Arachidonic Acid; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dinoprost; Eicosanoids; Endothelium, Vascular; Epoprostenol; Female; Fetal Blood; Gestational Age; Humans; Immunoenzyme Techniques; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Radioimmunoassay; Tritium; Umbilical Veins

The role of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) in the pathogenesis of hypertension and altered renal functions, which are the main symptoms of preeclampsia, has gained importance. Serum and urine samples of 59 women (24 preeclamptic pregnant (PEP), 20 normotensive pregnant (NTP) and 15 nonpregnant) were investigated by means of prostaglandin levels and urea, creatinine and creatinine clearance values. PEP patients, when compared with NTP patients, show a significant decrease in PGE2 and PGF2alpha levels (p < 0.01 and p < 0.05, respectively) accompanied by changes in some parameters of renal function such as serum urea, creatinine and creatinine clearance. Although disorders in prostaglandin levels may be responsible for some renal pathologic changes, renal functional and morphologic alterations may also result in abnormal prostaglandin activity.

Topics: Adult; Creatinine; Dinoprost; Dinoprostone; Female; Humans; Kidney; Metabolic Clearance Rate; Pre-Eclampsia; Pregnancy; Reference Values; Urea

To determine whether circulating markers of oxidative stress are elevated in pre-eclampsia when appropriate precautions are taken to prevent in vitro oxidation. A prospective study.. Nuffield Department of Obstetrics and Gynaecology, Oxford and The William Harvey Institute, London.. Three groups of women: those with pre-eclampsia (n = 19), control pregnant women (n = 19) matched for gestation, age and parity and a group of non pregnant individuals of reproductive age (n = 7).. Citrated plasma was stored at -80 degrees C with 20 micromol beta hydroxytoluene to prevent auto-oxidation. Plasma samples were assayed for levels of 8 epi-prostaglandin F2alpha, lipid hydroperoxides, malondialdehyde and also the lipid soluble antioxidant vitamin E.. There were no differences in 8 epi-prostaglandin F2alpha, lipid peroxide or malondialdehyde levels between the groups of women with pre-eclampsia and those acting as pregnant controls. However, lipid hydroperoxides and malondialdehyde were significantly raised in both pre-eclampsia and normal pregnancy, compared with nonpregnant women. Vitamin E levels were similar in women with pre-eclampsia and those with a normal pregnancy, but in both groups levels were significantly higher than in nonpregnant women.. Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.

Topics: Adult; Biomarkers; Dinoprost; Female; Humans; Lipid Peroxides; Malondialdehyde; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Vitamin E

This study was undertaken to observe the effects of organic or inorganic calcium antagonists and to investigate the involvement of cyclic nucleotides in regulating the vascular tone in the chorionic artery from normal or preeclamptic placenta. KCI and prostaglandin (PG) F2 alpha produced marked and constant contractions in chorionic arterial preparations of both normal and preeclamptic placentas. Nifedipine (NIF), verapamil (VER) and diltiazem (DIL) reduced the tension that had been produced by KCI and PGF2 alpha in a concentration-dependent fashion in both preparations, and the potency order of the three agents was NIF > VER > DIL. In preeclamptic arteries, however, the magnitudes of vasodilatation induced by NIF and DIL were much smaller than those in normal chorionic arteries. Mg2+ and Cd2+ also relaxed the tension induced by KCI and PGF2 alpha. In preeclamptic chorionic artery, the vasodilatation induced by Mg2+ was significantly potentiated, while that by Cd2+ was not. Removing endothelium did not alter cyclic GMP content in both preparations. In both preparations contracted by PGF2 alpha, nitroprusside markedly increased cyclic GMP content, but neither cyclic GMP nor cyclic AMP content was affected by acetylcholine, NIF, isopro-terenol, or Mg2+. The above results suggest that neither cyclic AMP nor cyclic GMP is involved in regulating the vascular tone of chorionic artery and that sensitivity of the artery in preeclampsia to the inhibitory action of calcium antagonist might be different from that in normal placenta.

Topics: Arteries; Calcium Channel Blockers; Cyclic AMP; Cyclic GMP; Dinoprost; Female; Humans; Placenta; Potassium Chloride; Pre-Eclampsia; Pregnancy; Vasoconstriction

1. This study was designed to seek evidence for excessive lipid peroxidation in pre-eclamptic women using 8-iso-prostane as a novel bioactive marker of lipid peroxidation in vivo. Plasma free, total and urinary 8-iso-prostane were measured in 20 women with proteinuric pre-eclampsia, and compared with 18 age- and gestation-matched pregnant control subjects, before delivery and at 6 weeks post-partum. 2. Plasma free 8-iso-prostane was significantly elevated in the pre-eclamptic women compared with control subjects before delivery, and fell to control levels post-partum. Conversely, levels in women with normal pregnancy rose post-partum. 3. Total plasma 8-iso-prostane levels were not significantly elevated in pre-eclamptic women compared with control subjects during pregnancy, but fell significantly in the pre-eclamptic women post-partum, suggesting that they had relatively higher levels compared with their non-pregnant state. 4. Urinary 8-iso-prostane excretion was significantly lower in the pre-eclamptic women compared with control subjects during pregnancy, suggesting that renal clearance of 8-iso-prostane is impaired in pre-eclampsia. 5. Increased levels of plasma free 8-iso-prostane in pre-eclampsia could be due to an increase in lipid peroxidation, an increase in phospholipase A2 activity or a reduction in renal clearance of 8-iso-prostane, or a combination of all three. The potent direct and indirect vasoconstrictor actions of 8-iso-prostane may contribute to the pathogenesis of pre-eclampsia.

Topics: Adult; Biomarkers; Dinoprost; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Postpartum Period; Pre-Eclampsia; Pregnancy

This study characterises the reactivity of chorionic plate artery in pre-eclampsia to prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), and potassium chloride (KCl) and examines the role of the vascular endothelium in these responses. Ring segments of the chorionic plate arteries of women after normal and pre-eclamptic pregnancies were contracted by PGF2 alpha, 5-HT, and KCl. The experiments were carried out in the presence and absence of endothelium, and on intact rings treated with 10(-6)M indomethacin. The maximal contractile responses of rings from pre-eclamptic women to 5-HT, PGF2 alpha, or KCl were significantly greater than those of rings from normotensive pregnant women. The EC50 values of responses were significantly lower in rings from pre-eclamptic subjects. Endothelium removal and treatment of the rings with indomethacin had no effect on the contractile responses of rings from normotensive pregnant women to all the agents, but significantly increased the EC50 value and decreased the maximal contractile responses of rings from pre-eclamptic women to 5-HT and PGF2 alpha. While de-endothelialisation increased the EC50 value for responses of the rings from pre-eclamptic women to KCl, pretreatment with indomethacin did not significantly affect the KCl-induced responses. The results of the study suggest that pre-eclampsia enhanced the reactivity of human chorionic plate artery to 5-HT, PGF2 alpha, and KCl through the involvement of endothelial derived contracting factors. The increased responses to 5-HT and PGF2 alpha were inhibited by indomethacin, but those to KCl were not.

Topics: Arteries; Chorion; Dinoprost; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Humans; Indomethacin; Potassium Chloride; Pre-Eclampsia; Pregnancy; Serotonin; Vasoconstriction

This study examined the activity of sodium nitroprusside (SNP) in the human fetal-placental circulation in vitro in pathological and experimental conditions in which vascular function may be impaired. SNP (13-3400 nM) caused a concentration-dependent reduction in fetal arterial perfusion pressure (FAP) in Krebs' perfused placental cotyledons, at basal tone and following pre-constriction with prostaglandin F2 alpha (PGF2 alpha). SNP-induced reduction in FAP in the PGF2 alpha pre-constricted fetal-placental circulation was enhanced approximately six-fold (5.85) in those placentae pre-treated with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (100 microM). Reductions in FAP in the preconstricted fetal-placental vasculature caused by SNP were not altered by prior infusion of ouabain (100 nM) into the fetal circulation or during low oxygen perfusion (O2 tension < 50 mmHg). No differences were observed in the responses obtained to SNP in placentae obtained from women with normotensive pregnancies or those associated with (i) pregnancy-induced hypertension, (ii) intra-uterine growth retardation, or (iii) an elevated umbilical-artery Doppler-ultrasound systolic/diastolic ratio, in either preconstricted placentae or those at basal tone. These findings are consistent with an up-regulation of guanylate cyclase/cGMP-mediated vasodilatation in the fetal-placental vasculature following complete blockade of endogenous NO production.

Topics: Adolescent; Adult; Arginine; Blood Pressure; Dinoprost; Enzyme Inhibitors; Female; Fetal Growth Retardation; Fetus; Humans; Hypertension; In Vitro Techniques; Nitric Oxide Synthase; Nitroarginine; Nitroprusside; Ouabain; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Vasoconstriction; Vasodilation

The aim of our study was to assess the efficacy of labor induction among patients affected by EPH gestosis after intracervical extra-amniotic insertion of 15 mg PGF2 alpha in methyl-cellulose gel. We concluded that PGF2 alpha when given intracervically in methyl-cellulose gel is a highly effective inducer of cervical ripening process as well as subsequent uterine contractions, too. It should be stressed that in no case did we find blood pressure increase after such therapy.

Topics: Adult; Cervix Uteri; Dinoprost; Female; Gels; Humans; Labor, Induced; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

The hypothesis that preeclampsia may be associated with an increase in the response of the placental arteries to vasoconstrictors or a decrease in their response to vasodilators was tested.. Concentration-response curves to various agents were determined on helical strips of fetal placental arteries from normotensive (n = 33) and preeclamptic (n = 8) women to calculate the potencies and maximal effects of the agents.. Endothelin, prostaglandin F2 alpha, and serotonin caused concentration-dependent contractions; angiotensin II and norepinephrine produced little or no effects. The prostacyclin analog iloprost and atrial natriuretic factor, but not isoproterenol, relaxed placental arteries. Iloprost was more effective on preeclamptic than on normal arteries, but the effects of other agents on the two groups of arteries did not differ. Placental arteries exhibited spontaneous oscillations that were more marked in preeclamptic than in normal arteries and were inhibited by indomethacin.. Preeclampsia is not associated with an increase in the responses of fetal placental arteries to vasoconstrictors or a decrease in their response to vasodilators. However, placental arteries from preeclamptic subjects exhibit increased oscillations.

Topics: Adult; Angiotensin II; Arteries; Atrial Natriuretic Factor; Dinoprost; Endothelins; Female; Humans; Iloprost; Isoproterenol; Norepinephrine; Placenta; Pre-Eclampsia; Pregnancy; Serotonin; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

The plasma levels of prostaglandins A, E, and F2 alpha were measured by the radioimmunoassay in 146 hypertensive and 62 healthy pregnant females. It was ascertained that beginning in the second trimester, the ratio of various prostaglandins is impaired in the direction of increasing values of substances from the pressor group as the hypertensive disease evolves. This is due to lower levels of prostaglandins A and E and/or higher levels of prostaglandins F2 alpha. In associated late gestosis, prostaglandin levels are related to the clinical manifestations of this disease. There are increased prostaglandin F2 alpha concentrations with severe nephropathy. The studies indicate that prostaglandins affect the course of hypertensive disease in pregnant women and the development of associated late gestosis.

Topics: Dinoprost; Female; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Prostaglandins; Prostaglandins A; Prostaglandins E

Prostaglandin E2 (PGE2), Prostaglandin F2 alpha (PGF2 alpha),6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) were measured with radioimmunoassay in placentae of 18 normotensive and 22 moderate or severe PIH gravidae. The content of PGE2 and PGF2 alpha did not change significantly in placentae of PIH patients suggesting that PGE2 and PGF2 alpha in placenta were not important in causing PIH. The content of placental 6-keto-PGF1 alpha also showed no significant difference, while TXB2 levels were significantly higher in PIH patients. The 6-keto-PGF1 alpha/TXB2 in PIH patients was remarkably lower than in normotensive women. These results indicate that an increase in TXB2 level and thus a decrease in the ratio of 6-keto-PGF1 alpha to TXB2 of placenta may be a pathogenetic factor in PIH.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Dinoprost; Dinoprostone; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Radioimmunoassay; Thromboxane B2

Biochemical and biophysical properties of umbilical arteries from normotensive and preeclamptic pregnancies were examined. The production of prostaglandins E and F, 6-keto-PGF1 alpha, and thromboxane B2 by umbilical arteries from normotensive, mildly preeclamptic, and severely preeclamptic pregnancies were measured in incubation media at baseline and after addition of arachidonic acid. The initial baseline values of 6-keto-PGF1 alpha were decreased in the severely preeclamptic patients with intrauterine growth retardation (IUGR) but not in any of the other groups. Addition of arachidonic acid resulted in a significant increase in 6-keto-PGF1 alpha production over initial baseline in all groups except in the severely preeclamptic pregnancies without IUGR. These results suggest a differential defect in the 6-keto-PGF1 alpha metabolic pathway in severely preeclamptic patients with IUGR compared with those without IUGR. The stretch response curve to serotonin was decreased in the severely preeclamptic group with IUGR compared with the control group. The contractile response to individual vasoactive agents (serotonin, prostaglandin F2, norepinephrine, angiotensin II, and arachidonic acid) showed no significant difference between the normotensive and preeclamptic groups.

Topics: Angiotensin II; Arachidonic Acid; Arachidonic Acids; Dinoprost; Female; Fetal Growth Retardation; Humans; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Pre-Eclampsia; Pregnancy; Prostaglandins; Prostaglandins F; Serotonin; Umbilical Arteries

Plasma 6-keto prostaglandin F1 alpha, 13,14-dihydro-15-keto prostaglandin F, and thromboxane B2 levels were measured in normotensive and preeclamptic patients during pregnancy and the postpartum period. From 30 to 40 weeks of gestation, 6-keto prostaglandin F1 alpha levels of preeclamptic patients were significantly lower than those of normotensive women; 13,14-dihydro-15-keto prostaglandin F and thromboxane B2 concentrations in preeclamptic patients did not significantly differ from those of the normotensive group. At delivery, 6-keto prostaglandin F1 alpha levels of maternal and umbilical venous plasma of preeclamptic women were also significantly lower than those of normotensive women. In the postpartum period these three prostanoids were not significantly different in normotensive women compared to preeclamptic women, with clinical preeclamptic symptoms soon disappearing in most of our patients. From the results, it seems that prostacyclin plays an important role in preeclampsia.

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprost; Female; Fetal Blood; Humans; Labor, Obstetric; Postpartum Period; Pre-Eclampsia; Pregnancy; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Thromboxanes

In the present studies, spontaneously hypertensive rats (SHR) were used as the experimental model of hypertension in pregnancy. Systolic blood pressure of the NaCl loading group was maintained in a hypertensive state throughout pregnancy, probably because of NaCl retention, whereas that of the control group fell in the last stage of gestation. Urinary kallikrein levels, prostaglandin F2 alpha main urinary metabolite (PGF-MUM), plasma renin activity and plasma aldosterone concentration were determined both in the control group and the NaCl loading group. The results suggested that the NaCl loading group successfully preserved negative feed back in the kallikrein-kinin system, prostaglandin system and renin-angiotensin-aldosterone system as the blood pressure regulation mechanism. Fetal prognosis was poor in the NaCl loading group, because the incidence of SFD and fetal death rate were significantly higher than those of the control group. These findings, including histological observations, were similar to those of hypertensive pregnancy in human subjects reported in recent studies, and suggested that NaCl was closely related to hypertension in pregnancy.

Topics: Animals; Blood Pressure; Diet, Sodium-Restricted; Dinoprost; Electrolytes; Female; Hypertension; Kallikreins; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins F; Rats; Rats, Inbred SHR; Renin; Sodium Chloride

Topics: Abortion, Habitual; Animals; Dinoprost; Female; Humans; In Vitro Techniques; Muscle, Smooth; Obstetric Labor Complications; Pre-Eclampsia; Pregnancy; Prostaglandins F; Rats; Uterine Contraction

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.

Topics: Aldosterone; Dinoprost; Dinoprostone; Epinephrine; Female; Humans; Hypertension; Norepinephrine; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins; Prostaglandins E; Prostaglandins F; Reference Values; Renin

Topics: Abortion, Habitual; Animals; Dinoprost; Female; Guinea Pigs; Humans; Membrane Potentials; Muscle Contraction; Muscle, Smooth; Pre-Eclampsia; Pregnancy; Prostaglandins F; Rats

Topics: Dinoprost; Dinoprostone; Female; Humans; Pre-Eclampsia; Pregnancy; Prostaglandins E; Prostaglandins F

The concentrations of prostaglandins E (PGE) and F (PGF), 13, 14-dihydro-15-oxo-prostaglandin F (PGFM) and thromboxane B2 (TXB2) were measured by specific radioimmunoassays in tissues obtained from women with and without pre-eclampsia. The concentrations of PGE in the amnion, chorion, decidua and placenta obtained from subjects with pre-eclampsia were significantly lower than those from subjects without pre-eclampsia. The concentration of PGE in these tissues increased significantly with gestational age and correlated with urinary oestrogen excretion. PGF concentrations were lower in the amnion and placenta of the pre-eclamptics compared to those without pre-eclampsia. The concentrations of PGFM in the amnion, decidua, and myometrium were lower in the pre-eclamptics. No significant difference in the TXB2 concentrations between the two groups of subjects were found. It is suggested that the altered tissue concentrations of prostaglandins in pre-eclamptics are due to the effects of gestational age and oestrogens and may or may not be involved in the pathogenesis of pre-eclampsia.

Topics: Adolescent; Adult; Amnion; Chorion; Decidua; Dinoprost; Female; Humans; Myometrium; Placenta; Pre-Eclampsia; Pregnancy; Prostaglandins E; Prostaglandins F; Thromboxane B2; Thromboxanes