Plasma protein carbonyls in nonpregnant, healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women. Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy nonpregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis. Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls. The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

Preeclampsia inactivates glucose-6-phosphate dehydrogenase and impairs the redox status of erythrocytes and fetal endothelial cells

Inactivation of glucose-6-phosphate dehydrogenase (G6PD) may contribute to vascular dysfunction in preeclampsia, and oxidative stress has been implicated in the pathogenesis of this disease. We have compared the susceptibility of erythrocytes and human umbilical vein endothelial cells (HUVEC) to oxidative stress in women with normotensive or preeclamptic pregnancies. The redox status of erythrocytes was also correlated with neutrophil-mediated superoxide (O₂⁻) production in women recruited to the “Vitamins in Preeclampsia” (VIP) trial. Erythrocytes and HUVEC from women with preeclampsia demonstrated impaired redox regulation and diminished response to glucose, detectable at 14–20 weeks gestation prior to onset of the clinical disease. Hexokinase and G6PD activities were decreased in erythrocytes and G6PD activity was decreased in HUVEC from preeclamptic pregnancies. Phorbol-ester-stimulated O₂⁻ was enhanced in preeclamptic neutrophils. Impaired redox regulation in erythrocytes and HUVEC in preeclampsia may be due to diminished hexokinase and G6PD activities resulting from increased release of reactive oxygen species from activated neutrophils. Our findings provide the first evidence that decreased G6PD activity in preeclampsia is associated with impaired redox regulation in erythrocytes and fetal endothelial cells. The deficiency in G6PD in preeclampsia potentially accounts for the lack of protection against oxidative stress afforded by antioxidant vitamin C/E supplementation in the VIP trial.     

Coenzyme Q10 is increased in placenta and cord blood during preeclampsia

Preeclampsia is a common (approximately 7% of all pregnancies) disorder of pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the levels of coenzyme Q(10) (CoQ(10)) in placental tissue compared to maternal and umbilical cord levels both during normal pregnancy and in those complicated with preeclampsia. Pregnant women (n = 30) and women with preeclampsia (n = 30) were included. Maternal, newborn cord blood levels and placental content of coenzyme Q(10) were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q(10) levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ(10) content in placenta from women with preeclampsia (mean 0.28 SEM 0.11 nmol/mg protein) was significantly higher compared to normal pregnancy (mean 0.09 SEM 0.01 nmol/mg protein; p = 0.05). Levels of CoQ(10) in cord blood from normal pregnant women (mean 0.30 SEM 0.05 micromol/l) were significantly lower than in preeclamptic women (mean 4.03 SEM 2.38 micromol/l). In conclusion, these data indicate a possible involvement of CoQ(10) in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated.     

Ambulatory Blood Pressure Monitoring for the Early Identification of Hypertension in Pregnancy

Gestational hypertension and preeclampsia are major contributors to perinatal morbidity and mortality. The diagnosis of gestational hypertension still relies on conventional clinic blood pressure (BP) measurements and thresholds of ≥140/90?mm Hg for systolic (SBP)/diastolic (DBP) BP. However, the correlation between BP level and target organ damage, cardiovascular disease risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than clinic BP measurement. Accordingly, ABPM has been suggested as the logical approach to overcoming the low sensitivity and specificity of clinic BP measurements in pregnancy. With the use of ABPM, differing predictable BP patterns throughout gestation have been identified for clinically healthy and hypertensive pregnant women. In normotensive pregnancies, BP steadily decreases up to the middle of gestation and then increases up to the day of delivery. In contrast, women who develop gestational hypertension or preeclampsia show stable BP during the first half of pregnancy and a continuous linear BP increase thereafter until delivery. Epidemiologic studies have also consistently reported sex differences in the 24-h patterns of ambulatory BP and heart rate. Typically, men exhibit a lower heart rate and higher BP than women, the differences being larger for SBP than DBP. Additionally, as early as in the first trimester of gestation, statistically significant increased 24-h SBP and DBP means characterize women complicated with gestational hypertension or preeclampsia compared with women with uncomplicated pregnancies. However, the normally lower BP in nongravid women as compared with men, additional decrease in BP during the second trimester of gestation in normotensive but not in hypertensive pregnant women, and significant differences in the 24-h BP pattern between healthy and complicated pregnancies at all gestational ages have not been taken into consideration when establishing reference BP thresholds for the diagnosis of hypertension in pregnancy. Several studies reported that use of the 24-h BP mean is not a proper test for an individualized early diagnosis of hypertension in pregnancy defined on the basis of cuff BP measurements, thus concluding that from such an awkward approach ABPM is not useful in pregnancy. The 24-h BP pattern that characterizes healthy pregnant women at all gestational ages suggests the use for diagnosis of a time-specified reference limit reflecting that mostly predictable BP variability. Once the time-varying threshold, given, for instance, by the upper limit of a tolerance interval, is available, the hyperbaric index (HBI), as a determinant of BP excess, can be calculated as the total area of any given subject's BP above the threshold. This tolerance-hyperbaric test, where diagnosis of gestational hypertension is based on the HBI calculated with reference to a time-specified tolerance limit, has been shown to provide high sensitivity and specificity for the early identification of subsequent hypertension in pregnancy, as well as a valuable approach for prediction of pregnancy outcome. ABPM during gestation, starting preferably at the time of the first obstetric check-up following positive confirmation of pregnancy, provides sensitive endpoints for use in early risk assessment and guide for establishing prophylactic or therapeutic intervention, and should thus be regarded as the required standard for the diagnosis of hypertension in pregnancy. (Author correspondence: rhermida@uvigo.es)     

Plasma protein carbonyls in nonpregnant,healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women.

Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy non-pregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis.

Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls.

The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

Immunohistochemical expression of von Willebrand factor in the preeclamptic placenta

Preeclampsia is a high-prevalence systemic pregnancy disorder associated with maternal and foetal mortality. Its pathogenesis is unknown, but it is thought that oxidative stress and endothelial dysfunction may play a fundamental role. Von Willebrand factor (vWF), a marker of endothelial cell injury, can be found in different cells and zones of the placenta. To determine the differential immunoexpression of vWF at different tissue types of preeclamptic placenta and endothelial dysfunction markers at maternal serum of preeclamptic pregnancies. A case–control study was performed on a population of pregnant women with preeclampsia (n = 14), and normal pregnancies (n = 8). Placental and blood plasma samples were withdrawn at delivery. Immunohistochemical vWF expression in the placental tissue was determined. Endothelial dysfunction was assessed through plasminogen activator inhibitor (PAI) 1 and 2 ratio and vWF concentration in maternal plasma. P values less than 0.05 were considered statistically significant. Preeclamptic women showed increased plasma PAI-1/PAI-2 ratio (P < 0.05). There was diminished placental vWF expression in syncytiotrophoblast and increased in the intervillous space of preeclamptic placentas (P < 0.05). No significant differences in vWF expression were found in the villous endothelium and stroma, but it was significantly higher in maternal plasma (P < 0.05). In preeclampsia occurs endothelial damage and placental cell injury. Cell damage in syncytiotrophoblast that occurs in preeclampsia could liberate vWF from syncytiotrophoblast to the placental intervillous space, and this may have pathogenic implications.     

Three-dimensional spheroidal culture of cytotrophoblast cells mimics the phenotype and differentiation of cytotrophoblasts from normal and preeclamptic pregnancies

Normal placental development is dependent on the orchestrated differentiation of cytotrophoblast (CTB) cells. This study was aimed at studying cytotrophoblast cells from normal and preeclamptic pregnancies in a three-dimensional spheroid-based cell culture model. First trimester cytotrophoblast cells cultured as spheroids maintain their high proliferative and invasive phenotype and respond to different cytokines upon stimulation in a three-dimensional invasion assay. In contrast, third trimester cytotrophoblast spheroids maintain their quiescent nonproliferating phenotype and invasion can only be induced by EGF. Contrasting the regular spheroidal arrangement of cytotrophoblast cells from normal third trimester pregnancies, spheroidal organization of preeclamptic cytotrophoblast cells is disturbed and the cells downregulate CD105 in vivo and in vitro. Furthermore, the invasion of both normal and preeclamptic third trimester, but not first trimester cytotrophoblast cells, is inhibited by pro-inflammatory cytokines. Plasma samples from pregnant women with preeclampsia significantly stimulate the invasion of first trimester cytotrophoblast cells and the sprouting of human umbilical vein endothelial cells (HUVECs) compared to plasma samples from healthy pregnant women. Taken together, the data establish the spheroidal cytotrophoblast model as a powerful system to mimic the in vivo phenotype of first and third trimester and preeclamptic cytotrophoblast cells and demonstrate that plasma-derived factors modulate the differentiation of cytotrophoblast cells.     

Increased urinary excretion of nephrin, podocalyxin, and βig-h3 in women with preeclampsia

Emerging evidence has shown that podocyte injury and reduced specific podocyte protein expressions contribute to proteinuria in preeclampsia. We collected urine specimens from women with preeclampsia to study whether podocyte-specific protein shedding is associated with renal barrier dysfunction. Urine specimens from women with normal pregnancies and from pregnant women complicated by chronic hypertension were used for comparison. We determined soluble podocyte slit protein nephrin levels in the urine specimens. Podocalyxin, βig-h3, and VEGF concentrations were also measured. We found that nephrin and podocalyxin were barely detectable in the urine specimens from normal pregnant women and from women with chronic hypertension. In preeclampsia, urinary nephrin and podocalyxin concentrations were significantly increased and highly correlated to each other, r(2) = 0.595. Nephrin and podocalyxin were also correlated with urine protein concentrations. βig-h3 was detected in the urine specimens from women with preeclampsia, and it is highly correlated with nephrin and podocalyxin concentrations in preeclampsia. βig-h3 was undetectable in normal pregnancy and pregnancy complicated by chronic hypertension. Elevated VEGF levels were also found in women with preeclampsia compared with those of normal pregnancy and pregnancy complicated by chronic hypertension. These results provide strong evidence that podocyte protein shedding occurs in preeclampsia, and their levels are associated with proteinuria. The finding of urinary βig-h3 excretion in preeclampsia suggests that increased transforming growth factor activity might also be involved in the kidney lesion in this pregnancy disorder.     

A Prospective Study of Selenium Concentration and Risk of Preeclampsia in Pregnant Iranian Women: a Nested Case–Control Study

Preeclampsia remains a leading cause of maternal and perinatal mortality and morbidity worldwide; however, its specific etiology still remains obscure. Some studies implicate poor maternal selenium status predisposing the mother to preeclampsia. This study was designed to determine changes in plasma selenium levels in women having preeclampsia as compared with those with normal pregnancy. In a nested case–control study, 650 normal primigravida in their first 24–28 weeks participated in the study. After 3 months of follow-up of all subjects, blood selenium levels were measured in 38 women presenting consecutively with preeclampsia and in 38 women having a normal pregnancy by atomic absorption spectrophotometry. Birth outcomes were recorded, such as gestational age at delivery, height, weight, birth head circumflex and 1-min Apgar score. Preeclampsia affects about 5.84 % of pregnancies, and in our study, there were no significant differences in age, anthropometric indices, and family history of preeclampsia between the preeclamptic and control groups. The selenium concentrations in plasma in women with preeclampsia were significantly lower as compared with those in women with normal pregnancy (70.63?±?21.41 versus 82.03?±?15.54 μg/L, p?<?0.05). Being in the bottom tertile of selenium concentration (less than 62.2 μg/L) was associated with greater risk of preeclampsia in pregnant women. The reduced selenium in the maternal circulations observed in the preeclamptic mothers support the hypothesis that insufficient selenium concentration may be a contributing factor to the pathophysiological mechanisms associated with preeclampsia, and optimizing the dietary selenium intake through supplementation could produce demonstrable clinical benefits.     

Sera from preeclamptic patients contain factor(s) that stimulate prostacyclin production by human endothelial cells.

A relative decrease in endothelial cell prostacyclin production may be pivotal in the genesis of preeclampsia. We determined the effect of sera from preeclamptic women on prostacyclin production by monolayers of normal term human umbilical vein endothelial cells. Endothelial cells were incubated with media containing serum from patients with preeclampsia, non-hypertensive, gestational age-matched pregnant controls, or normal non-pregnant controls (N = 7, all groups). 6-Keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, was measured directly in the culture medium by radioimmunoassay. Treatment with preeclamptic sera, when associated with a statistically significant increase in prostacyclin metabolite production by endothelial cells. Thus, sera from women with preeclampsia stimulate rather than inhibit prostacyclin production by endothelial cells. We speculate that there is a factor in the sera of women with preeclampsia that functions to activate endothelial cells or which may play a role in the homeostatic mechanisms to balance reduced prostacyclin output in preeclampsia.     

Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia

Preeclampsia is a pregnancy-specific syndrome and a major cause of maternal mortality. The pathophysiology of preeclampsia is unknown, and no proteome analysis of preeclampsia has been reported. We sought to identify proteins associated with preeclampsia using a proteomic technique and performed two-dimensional electrophoresis (2-DE) on sera from six patients with preeclampsia and six normal pregnant women, followed by comparison of the SYPRO Ruby-stained 2-DE profiles. A group of overexpressed spots was identified in the limited study set. Overexpressed spots were identified as clusterin by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) followed by peptide mass fingerprinting, a protein database search, and Western blot analysis. Additionally, sera of 80 preeclamptic women and 80 normal pregnant women were processed by immunoassay methods to confirm changes in clusterin concentrations quantitatively. Immunoassays showed that clusterin levels in the 80 preeclamptic women were significantly higher than those in the 80 controls (mean +/- SD; 1.62 +/- 0.46 times reference level in preeclamptic women vs. 1.30 +/- 0.46 times reference level in controls, P < 0.001). Proteomic analysis of serum proteins is a promising tool for studying preeclampsia pathophysiology and identifying proteins associated with preeclampsia.     

Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia.

AIM: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. METHODS: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37-38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at -20 degrees C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at -80 degrees C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at -80 degrees C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. RESULTS: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. CONCLUSIONS: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.     

Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels

Preeclampsia is a common ( approximately 7% of all pregnancies) disorder of human pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the concentration of coenzyme Q10 in normal pregnancy and preeclampsia. Pregnant women (n = 18), women with preeclampsia (n = 12), and nonpregnant normotensive women (n = 22) were included. Plasma levels of coenzyme Q10 were measured by high-performance liquid chromatography. Plasma coenzyme Q10 levels were significantly higher in normal pregnant women (mean = 1.08, SEM = 0.08 umol/l; p <.005) in comparison to nonpregnant women (mean = 0.86, SEM = 0.16 umol/l) and women with preeclampsia (mean = 0.7, SEM = 0.03 umol/l; p <.0001). These results demonstrated that during preeclampsia there is a significant decrease in plasma levels of coenzyme Q10 compared to normal pregnant women, and compared to those who are not pregnant.     

The role of adiponectin in placentation and preeclampsia

Preeclampsia is not fully understood; and few biomarkers, therapeutic targets, and therapeutic agents for its management have been identified. Original investigative findings suggest that abnormal placentation triggers preeclampsia and leads to hypertension, proteinuria, endothelial dysfunction, and inflammation, which are characteristics of the disease. Because of the regulatory roles that it plays in several metabolic processes, adiponectin has become a cytokine of interest in metabolic medicine. In this review, we have discussed the role of adiponectin in trophoblast proliferation, trophoblast differentiation, trophoblast invasion of the decidua, and decidual angiogenesis, which are the major phases of placentation. Also, we have highlighted the physiological profile of adiponectin in the course of normal pregnancy. Moreover, we have discussed the involvement of adiponectin in hypertension, endothelial dysfunction, inflammation, and proteinuria. Furthermore, we have summarized the reported relationship between the maternal serum adiponectin level and preeclampsia. The available evidence indicates that adiponectin level physiologically falls as pregnancy advances, regulates placentation, and exhibits protective effects against the symptoms of preeclampsia and that while hyperadiponectinemia is evident in normal-weight preeclamptic women, hypoadiponectinemia is evident in overweight and obese preeclamptic women. Therefore, the clinical use of adiponectin as a biomarker, therapeutic target, or therapeutic agent against the disease looks promising and should be considered.     

Maternal plasma VEGF, sVEGF-R1, and PlGF concentrations in preeclamptic and normotensive pregnant Zimbabwean women

Vascular endothelial growth factor (VEGF), a disulphide-linked homodimeric glycoprotein that is selectively mitogenic for endothelial cells, plays an important role in vasculogenesis and angiogenesis. Preeclampsia, a relatively common complication of pregnancy that is characterized by diffuse endothelial dysfunction possibly secondary to impaired trophoblast invasion of the spiral arteries during implantation, has recently been associated with alterations in maternal serum/plasma concentrations of VEGF, and other related growth factors and their receptors. We examined the relationship of maternal plasma VEGF, sVEGF-R1 and PlGF levels to the risk of preeclampsia among women delivering at Harare Maternity Hospital, Zimbabwe. 131 pregnant women with preeclampsia and 175 controls were included in a case-control study. Maternal plasma concentrations of each biomarker were measured using enzymatic methods. We used logistic regression to calculate odds ratios (OR) and 95 % confidence intervals (CI). Preeclampsia risk was inversely related with quartiles of plasma VEGF (OR: 1.0, 1.0, 0.7, and 0.5, with the lowest quartile as reference; p for trend=0.06). We noted a strong positive association between preeclampsia risk and sVEGF-R1 concentrations (OR: 1.0, 6.5, 9.7, 31.6, with the first quartile as the referent group; p for trend<0.001). After adjusting for confounders, we noted that women with sVEGF-R1 concentrations in the highest quartile (>or=496 pg/ml), as compared with those in the lowest quartile (<62 pg/ml) had a 31.6-fold increased risk of preeclampsia (OR=31.6, 95 % CI 7.7-128.9). There was no clear evidence of a linear relation in risk of preeclampsia with PlGF concentrations. In conclusion, plasma VEGF, sVEGF-R1 and PlGF concentrations (measured at delivery) were altered among Zimbabwean women with preeclampsia as compared with normotensive women. Our results are consistent with some, though not all, previous reports. Prospective studies are needed to: 1) identify modifiable determinants of maternal plasma concentrations VEGF, sVEGF-R1, and PlGF; and 2) evaluate the temporal relationship between observed alterations of these biological markers in preeclamptic pregnancies.     

Involvement of placental peptidases associated with renin-angiotensin systems in preeclampsia

Preeclampsia is characterized by pregnancy-induced hypertension accompanied with protein urea and generalized edema. Preeclampsia develops during the second half of pregnancy and resolves postpartum promptly, implicating the placenta as a primary cause in the disorder. Normal pregnancy is associated with reductions in arterial pressure and attenuated pressor response to exogenous infused angiotensin II (ANG II). In contrast, women with preeclampsia show the similar sensitivity to the pressor effect of ANG II as do non-pregnant women. To elucidate the involvement of placental peptidases associated with renin-angiotensin systems, we determined the localization of angiotensin-converting enzyme (ACE) and aminopeptidase A (AP-A), ANG II degrading enzyme, in the placenta and compared the expression of mRNA and protein in uncomplicated and preeclamptic placenta. In addition, AP-A expression in trophoblastic cells treated with ANG II and ACE expression in HUVECs under hypoxic condition were analyzed, respectively. The expression of both peptidases in the preeclamptic placenta was significantly higher than those from uncomplicated. ACE was primarily localized to venous endothelial cells of stem villous whereas AP-A expression was recognized in the trophoblast and pericytes of fetal arterioles and venules within stem villous. Hypoxia induced ACE expression in HUVECs while both hypoxia and ANG II evoked AP-A expression in trophoblast. These results suggested that hypoxic condition in preeclampsia induces ACE activation in feto-placental unit to maintain the fetal hemodynamics and placental AP-A plays a role as a component of the barrier of ANG II between mother and fetus.     

Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy

Increased cardiac output in pregnancy is associated with cardiac remodeling and possible reduction in contractility, which may worsen in preeclampsia. Left ventricular (LV) geometry and function were compared between nonpregnant controls (n = 12) and normotensive (n = 44) and preeclamptic (n = 15) pregnant women using echocardiography. Load-independent comparisons of LV systolic function compared end-systolic stress (ESS) and rate-corrected velocity of circumferential fiber shortening (V(CFC)). Mean arterial pressures were 101 +/- 14 mmHg in preeclampsia, 76 +/- 6 mmHg in normotensive pregnancy, and 78 +/- 6 mmHg in controls (P < 0.005 vs. preeclampsia). LV mass increased during normotensive pregnancy (66 +/- 13 to 76 +/- 16 g/m(2); P < 0.05; controls, 65 +/- 10 g/m(2); P < 0.05) and was greater in preeclampsia (90 +/- 18 g/m(2); P < 0.05). In normotensive pregnancy, ESS decreased (59 +/- 9 to 52 +/- 11 g/cm(2); P < 0.05; controls, 66 +/- 14 g/cm(2); P < 0.005). ESS was greater in preeclampsia (60 +/- 14 g/cm(2); P < 0.05). In controls, there was an inverse relationship between ESS and V(CFC) (r = -0.78). The ESS-V(CFC) relationships in normotensive and preeclamptic pregnancy were unchanged from controls. We conclude that LV hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac work, and LV contractility is preserved.     

Pathophysiology of hypertension in response to placental ischemia during pregnancy: A central role for endothelin?

Background: Preeclampsia is new-onset hypertension with proteinuria during pregnancy. The initiating event in preeclampsia has been postulated to involve reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium.Objective: The main objective of this brief review was to highlight some of the recent advances in our understanding of the mechanisms whereby the endothelin (ET) system, via ET type A (ET_A) receptor activation, modulates blood pressure in preeclamptic women and in animal models of pregnancy-related hypertension.Methods: This review focused on the role of ET and tumor necrosis factor-α (TNF-α) in preeclampsia, with emphasis on the pathophysiology of hypertension in response to placental ischemia in animal models of pregnancy. Relevant published data were identified by searching PubMed and supplemented with contributions from our laboratory.Results: Studies in preeclamptic women indicate that their hypertension is associated with increases in ET synthesis. Recent studies in pregnant rats indicate that the ET system is activated in response to reductions in uterine perfusion pressure and to chronic elevations in serum TNF-α concentrations. In these 2 animal models, the findings also suggest that ET A receptor activation may play a role in mediating hypertension.Conclusions: Although recent studies in animal models implicate an important role for the ET system in preeclampsia, the usefulness of selective ET A receptor antagonists for the treatment of hypertension in women with preeclampsia remains unclear. This important question will not be answered until well-controlled clinical studies using specific ET A receptor antagonists are conducted for women with preeclampsia.