OBJECTIVETo investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism.

METHODSEighteen pregnant SD rats at day 12 of gestation were randomized equally into gestational hypertension model group, hemin treatment group, and normal pregnancy (control) group. In the former two groups, the rats were subjected to daily nitro-L-arginine methyl ester (L-NAME, 80 mg/kg) gavage since gestational day 14 for 7 consecutive days to induce gestational hypertension; saline was administered in the same manner in the control rats. The rats in hemin group received daily intraperitoneal injection of hemin (30 mg/kg) starting from gestational day 16. HO activity and carboxyhemoglobin (COHb) level in rat placental tissue were detected with spectrophotometric method, and soluble vascular endothelial growth factor receptor-1 (sFlt-1) and vascular endothelial growth factor (VEGF) level in the placental tissue homogenate supernatant were detected using ELSIA.

RESULTSAt gestational day 20, the blood pressure and 24-h urinary protein were significantly higher in the model group than in the other two groups (P<0.05), and were higher in hemin group than in the control group (P<0.05); HO activity and COHb content in the placenta tissue were the lowest in the model group (P<0.05), and was lower in hemin group than in the control group (P<0.05). The level of sFlt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups (P<0.05); sFlt-1 level remained higher and VEGF lower in hemin group than in the control group (P<0.05).

CONCLUSIONHemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFlt-1 and increasing VEGF in the placental tissue.

Animals ; Blood Pressure ; Carbon Monoxide ; metabolism ; Disease Models, Animal ; Female ; Heme Oxygenase (Decyclizing) ; Hemin ; pharmacology ; Hypertension, Pregnancy-Induced ; drug therapy ; Placenta ; drug effects ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

PURPOSE: Adiponectin and resistin are potent regulators of glucose homeostasis and energy metabolism. In this study, we aimed to determine (1) the role of gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) on the plasma levels of adiponectin and resistin in cord blood, and (2) the association of the hormones with anthropometric parameters at birth. METHODS: This study investigated 80 pregnant women at 26-41 weeks of gestation, including 46 healthy pregnant woman as controls; 14 women with GDM; and 20 women with PIH, and 80 newborn infants (36 male, and 44 female). The following anthropometric measurements were obtained: maternal weight, length, body mass index (BMI), neonatal birth weight, neonatal length, and ponderal index. Cord blood samples were obtained from 80 neonates at the time of delivery. Plasma adiponectin levels (RIA) and resistin levels (ELISA) were measured. RESULTS: Adiponectin levels were significantly lower in the fullterm group with GDM and fullterm group with PIH than the control group. Plasma resistin levels were significantly lower in the preterm and the fullterm groups with PIH than in the control group, and significantly higher in the fullterm group with GDM than in the PIH group. Similarly, adiponection was significantly lower in large for gestational age (LGA) infants than appropriate gestational age (AGA) and small for gestational age (SGA) infants, and resistin was significantly higher in LGA infants than in SGA infants. Adiponectin levels were negatively correlated with ponderal index, maternal HbA1c, and maternal body mass index (BMI). Plasma resistin levels were positively correlated with birth weight and maternal BMI. CONCLUSION: Alteration of adiponectin and resistin levels in cord blood of fetuses of women with GDM and PIH may influence the development of metabolic disorders at all stages of development.
Adiponectin ; Birth Weight ; Body Mass Index ; Diabetes, Gestational ; Energy Metabolism ; Female ; Fetal Blood ; Fetus ; Gestational Age ; Glucose ; Homeostasis ; Humans ; Hypertension, Pregnancy-Induced ; Infant ; Infant, Newborn ; Male ; Parturition ; Plasma ; Pregnancy ; Pregnancy Complications ; Pregnant Women ; Resistin

PURPOSE: Adiponectin and resistin are potent regulators of glucose homeostasis and energy metabolism. In this study, we aimed to determine (1) the role of gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) on the plasma levels of adiponectin and resistin in cord blood, and (2) the association of the hormones with anthropometric parameters at birth. METHODS: This study investigated 80 pregnant women at 26-41 weeks of gestation, including 46 healthy pregnant woman as controls; 14 women with GDM; and 20 women with PIH, and 80 newborn infants (36 male, and 44 female). The following anthropometric measurements were obtained: maternal weight, length, body mass index (BMI), neonatal birth weight, neonatal length, and ponderal index. Cord blood samples were obtained from 80 neonates at the time of delivery. Plasma adiponectin levels (RIA) and resistin levels (ELISA) were measured. RESULTS: Adiponectin levels were significantly lower in the fullterm group with GDM and fullterm group with PIH than the control group. Plasma resistin levels were significantly lower in the preterm and the fullterm groups with PIH than in the control group, and significantly higher in the fullterm group with GDM than in the PIH group. Similarly, adiponection was significantly lower in large for gestational age (LGA) infants than appropriate gestational age (AGA) and small for gestational age (SGA) infants, and resistin was significantly higher in LGA infants than in SGA infants. Adiponectin levels were negatively correlated with ponderal index, maternal HbA1c, and maternal body mass index (BMI). Plasma resistin levels were positively correlated with birth weight and maternal BMI. CONCLUSION: Alteration of adiponectin and resistin levels in cord blood of fetuses of women with GDM and PIH may influence the development of metabolic disorders at all stages of development.
Adiponectin ; Birth Weight ; Body Mass Index ; Diabetes, Gestational ; Energy Metabolism ; Female ; Fetal Blood ; Fetus ; Gestational Age ; Glucose ; Homeostasis ; Humans ; Hypertension, Pregnancy-Induced ; Infant ; Infant, Newborn ; Male ; Parturition ; Plasma ; Pregnancy ; Pregnancy Complications ; Pregnant Women ; Resistin

Animals ; Female ; Hypertension, Pregnancy-Induced ; metabolism ; pathology ; Kidney ; metabolism ; pathology ; Pregnancy ; Protein Kinase C-alpha ; genetics ; metabolism ; Rats ; Rats, Wistar ; Transcription, Genetic

To examine the changes in number and function of endothelial progenitor cells (EPCs) from peripheral blood (PB) in hypertension disorder complicating pregnancy (HDCP), 20 women with HDCP and 20 normal pregnant women at the third trimester were studied. Mononuclear cells (MNCs) from PB were isolated by Ficoll density gradient centrifugation. EPCs were identified by positive expression of both CD34 and CD133 under fluorescence microscope and positive expression of factor VIII as shown by immunocytochemistry. The number of EPCs was flow-cytometrically determined. Proliferation and migration of EPCs were measured by MTT assay and modified Boyden chamber assay, respectively. The adhesion activity of EPCs was detected by counting the number of the adherent cells. The results showed that, compared with normal pregnant women, the number of EPCs was significantly reduced in HDCP (4.29%+/-1.21% vs 15.32%+/-2.00%, P<0.01), the functional activity of EPCs in HDCP, such as proliferation (13.45%+/-1.68% vs 18.45%+/-1.67%), migration (37.25+/-7.28 cells/field vs 67.10+/-9.55 cells/field) and adhesion activity (20.65+/-5.19 cells/field vs 34.40+/-6.72 cells/filed) was impaired (P<0.01). It is concluded that the number and function of EPCs are significantly decreased in HDCP.
Antigens, CD/metabolism ; Antigens, CD34/metabolism ; Case-Control Studies ; Cell Adhesion ; Cell Count ; Cell Movement ; Endothelial Cells/pathology ; Endothelial Cells/*physiology ; Glycoproteins/metabolism ; Hypertension, Pregnancy-Induced/*pathology ; Peptides/metabolism ; Stem Cells/pathology ; Stem Cells/*physiology

Expression of endogenous ouabain in placenta and the concentrations of serum ET-1 and NO were examined in 30 patients with hypertensive disorder complicating pregnancy (HDCP) and 30 healthy pregnant women to investigate the effect of endogenous ouabain on HDCP. Compared with the healthy pregnant group, the expression of endogenous ouabain dramatically increased in the HDCP groups (P<0.01). There was a significantly positive correlation between the expression of endogenous ouabain with ET-1 (r=0.5567, P<0.01), while the correlation of endogenous ouabain and NO was significantly negative (r=-0.6895, P<0.01). As expected, the correlation between ET-1 and NO was negative (r=-0.7796, P<0.01). ET-1 concentrations of maternal and cord sera in HDCP groups were significantly higher in comparison with healthy pregnant group (P<0.01). On the contrast, NO concentrations were much lower in the maternal and cord sera of HDCP groups as compared with healthy pregnant group (P<0.01). Our data suggest that endogenous ouabain is directly involved in the nosogenesis of HDCP, with accompanying decreased NO and the elevated of ET-1.
Case-Control Studies ; Endothelin-1/*blood ; Hypertension, Pregnancy-Induced/*metabolism ; Nitric Oxide/*blood ; Ouabain/*metabolism ; Placenta/*metabolism

OBJECTIVE: To determine the apoptosis in placenta tissues of patients with hypertensive disorder complicating pregnancy and its relationship with Bcl-2, TGFbeta1, and to explore the etiology of hypertensive disorder complicating pregnancy. METHODS: Forty-five placenta samples were obtained from pregnancies with hypertensive disorder (15 gestational hypertension, 15 mild preeclampsia, and 15 severe preeclampsia) and 45 normal placenta tissues were enrolled from the third-trimester pregnancies. Immunohistochemistry (SP method) was used to study the expression of Bcl-2 and TGFbeta1 in human trophoblasts. Terminal deoxynucleotidyl transferase-dUTP nick end-labeling (TUNEL) was used to quantify the incidence of apoptosis in human trophoblasts. RESULTS: The apoptosis rate and TGFbeta1 expression in hypertensive disorder complicating pregnancy group was higher than that in the control group, but the Bcl-2 expression was significantly lower than the control group (all Ps<0.01). With the aggravation of this illness, the apoptosis rate and TGFbeta1 expression in the gestational hypertension group, mild preeclampsia group, and severe preeclampsia tended to be increasing, but the Bcl-2 expression was decreasing (P<0.001). The apoptosis of placenta villi and TGFbeta1 expression were positively correlated in the severe preeclampsia group and mild preeclampsia group,but the apoptosis of placenta villi and Bcl-2 were negatively correlated (all Ps<0.05). TGFbeta1 and Bcl-2 expressions in the severe preeclampsia group and mild preeclampsia group were negatively correlated (P<0.05). CONCLUSION Apoptosis of the placental trophoblasts of pregnancies with hypertensive disorder is evidently enhanced. The TGFbeta1 expression increases and the Bcl-2 expression decreases. The imbalance between TGFbeta1 and Bcl-2 expression may induce the hypertensive disorder.
Adult ; Apoptosis ; Female ; Humans ; Hypertension, Pregnancy-Induced ; metabolism ; Placenta ; cytology ; metabolism ; Pregnancy ; Pregnancy Trimester, Third ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the changes in serum levels of Th1- (IL-2 and TNF-alpha) and Th2-type cytokines (IL-10) and the ratios of Th1/Th2 (IL-2/IL-10 and TNF-alpha/IL-10) in preeclampsia and in gestational hypertension.

METHODSLevels of IL-2, IL-10 and TNF-alpha were determined with radioimmunoassay in serum samples from 22 women with preeclampsia, 15 women with gestational hypertension and 32 normal term pregnant women. The Th1/Th2 ratios were calculated accordingly.

RESULTThere were no significant differences in serum levels of IL-2, IL-10 and TNF-alpha (P>0.05 for all) among normal pregnancy, gestational hypertension and preeclampsia. The ratio of serum IL-2/IL-10 was significantly higher in preeclampsia than that in controls (P < 0.05), and the ratio of TNF-alpha/IL-10 significantly higher in patients with preeclampsia than that in either controls or gestational hypertension (P<0.025 for both).

CONCLUSIONAlterations of serum cytokine balance with predominance of Th1 immunity were observed in preeclampsia. These associations may offer insight into the pathogenesis of preeclampsia.

Adult ; Female ; Humans ; Hypertension, Pregnancy-Induced ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Pre-Eclampsia ; blood ; Pregnancy ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Tumor Necrosis Factor-alpha ; metabolism

The expression of transforming growth factor-beta1 (TGF-beta1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-beta1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-beta1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-beta1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-beta1 could be express in syncytiotrophoblast. The levels of TGF-beta1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P < 0.05), while the serum VCAM-1 was significantly lower than in normal group (P < 0.01). There was a significant positive correlation between the expression of TGF-beta1 in placental tissues and the serum VCAM-1 (r = 0.969, P < 0.01). It was concluded that the level of TGF-beta1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH.
Hypertension, Pregnancy-Induced/*metabolism ; Placenta/metabolism ; Transforming Growth Factor beta/*metabolism ; Transforming Growth Factor beta1 ; Vascular Cell Adhesion Molecule-1/*blood

OBJECTIVETo study the relationship between imbalanced synthesis of human chorionic gonadotropin (hCG) alpha and beta subunits and the pathology of pregnancy-induced hypertension (PIH).

METHODSTotal hCG, free alphahCG and betahCG were measured in serum samples collected from 60 cases of PIH and 30 normal gravid women by radioimmunoassay. The ratio of total hCG/betahCG, betahCG/FalphahCG, (FalphahCG+betahCG)/betahCG were calculated. Immunohistochemical staining was performed in 13 placenta from each group.

RESULTSIn PIH group the levels of FalphahCG, total hCG and betahCG were significantly higher than those of normal group (FalphahCG: 528 +/-421 IU/L compared with 222 +/-129 IU/L; betahCG: 39396 +/-6412 IU/L compared with 24265 +/-5575 IU/L; total hCG: 66597 +/-9294 IU/L compared with 36078 +/-4767 IU/L, all P<0.001). The betahCG/FalphahCG ratio in PIH was lower than that of normal group (91.23 +/-53.38 Compared with 119.4 +/-80.1, P<0.05); (FalphahCG+betahCG)/betahCG ratio and total hCG/betahCG ratio in two groups were (1.022 +/-0.026 compared with 1.015 +/-0.011; 1.802 +/-0.339 compared with 1.807 +/-0.258, respectively P>0.05). The immunohistochemical intensity of betahCG and FalphahCG in syncytiotrophoblast was significantly increased in 13 PIH compared with the control.

CONCLUSIONThese data suggested that the imbalanced synthesis of hCG alpha and beta subunits may cause hypertension.

Adult ; Chorionic Gonadotropin ; biosynthesis ; Chorionic Gonadotropin, beta Subunit, Human ; biosynthesis ; Female ; Glycoprotein Hormones, alpha Subunit ; biosynthesis ; Humans ; Hypertension, Pregnancy-Induced ; etiology ; metabolism ; Pregnancy