Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nitric oxide in hypoxic fetoplacental vasoconstriction (HFPV) was investigated using dually perfused human placental cotyledons. Standard medium (Earle's salt solution with added dextran and L-arginine) was equilibrated with 95 per cent O2 and 5 per cent CO2 (maternal side) and 94 per cent N2 and 6 per cent CO2 (fetal side). Part 1 consisted of perfusion for 1 h, then maternal perfusate equilibrated with a 95 per cent N2 and 5 per cent CO2 for 20 min (hypoxia), and then the original perfusion conditions resumed for 40 min. In part 2, this sequence was repeated with standard medium alone (n = 6), or with added N-nitro-L-arginine methyl ester (L-NAME) (n = 6), or L-NAME and nitroglycerin (n = 6). When standard medium was used throughout, basal fetal perfusion pressure (30 +/- 2 mmHg) and the hypoxia-induced increase in perfusion pressure (18 +/- 1 mmHg) did not change significantly between parts 1 and 2. L-NAME increased basal perfusion pressure from 33 +/- 3 to 56 +/- 2 mmHg whereas perfusion pressure remained unchanged with L-NAME and nitroglycerin or nitroglycerin alone. The hypoxic vasoconstriction observed during part 1 in the L-NAME (14 +/- 3 mmHg) and the L-NAME with nitroglycerin groups (18 +/- 2 mmHg) was abolished during part 2 (to - 4 +/- 1 and 0.4 +/- 0.5 mmHg, respectively) whereas nitroglycerin alone significantly blunted the response (21 +/- 3 to 6 +/- 1 mmHg). Results suggest that a reduction in basal NO release mediates hypoxic fetoplacental vasoconstriction in the perfused human placental cotyledon in vitro.
Placenta 1997 Nov
PMID:Role of the L-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction. 936 97

Reactive oxygen and nitrogen intermediates (ROI, RNI), such as superoxide anion, nitric oxide (NO) and peroxynitrite, are present in villous trophoblasts and mediate TNF-alpha-induced apoptosis in other cell types. We therefore proposed that ROI/RNI mediate cytokine-induced apoptosis of cultured villous cytotrophoblasts. Treatment of cultures of highly purified term cytotrophoblasts with TNF-alpha and IFN-gamma had no effect on NO synthase (NOS) protein expression measured by immunoblot analysis: iNOS was not expressed and eNOS expression was unaffected. NO production assessed by nitrite levels was below detection limits of the Griess reaction and the NOS inhibitors L-NAME and L-NMMA did not decrease cytokine-stimulated apoptosis. Trophoblasts produced ROI and expressed Cu/Zn superoxide dismutase (SOD) protein but neither was affected by cytokine treatment. ROI scavengers (exogenous SOD, ascorbic acid and butylated hydroxyanisole) also had no effect on cytokine-stimulated apoptosis. Nitrotyrosine immunoblot analysis indicated peroxynitrite production but again cytokines did not reproducibly alter expression patterns or band intensities. Exogenous peroxynitrite stimulated cytotrophoblast apoptosis but only at high levels (1000 microM). We conclude that, although present in cultured villous cytotrophoblasts, ROI/RNI are not induced by TNF-alpha and IFN-gamma and do not mediate cytokine-induced apoptosis.
Placenta 1999 May
PMID:The role of reactive nitrogen/oxygen intermediates in cytokine-induced trophoblast apoptosis. 1032 52

In this study, using the human placenta perfused in vitro with Krebs' bicarbonate solution, we have examined the effects of changes in oxygen tension on the vasoreactivity of fetal placental blood vessels to corticotropin releasing hormone (CRH). Vasodilatory responses to human synthetic CRH were measured during sub-maximal vasoconstriction of the fetal placental circulation with prostaglandin F(2alpha)(PGF(2alpha)) (1-100 micrometer). Decreases in fetal placental arterial perfusion pressure (FAP) were obtained with CRH under conditions of high oxygen or low oxygen tension, >/=450 mmHg and </=50 mmHg, respectively. Secretion of CRH into the maternal and fetal placental circulations was measured during changes in oxygen tension in normal placentae and placentae from abnormal pregnancies complicated by pre-eclampsia. The change from high to low oxygen perfusion resulted in a small increase in the basal perfusion pressure (21+/-3.6 to 28.3+/-2.6 mmHg; (P</= 0.001, Student's paired t -test). During high oxygen perfusion, CRH (0. 3-3000 p m) caused a concentration dependent reduction of the PGF(2alpha)induced increase in FAP. However, during low oxygen perfusion, the vasodilatory effects of CRH were completely inhibited (P</= 0.05, regression analysis, ANOVA). The effect of the NO synthase inhibitor l -nitro-omega-arginine methyl ester (l -NAME, 1-100 micrometer), on basal FAP during high and low oxygen conditions was also established. Low oxygen perfusion significantly attenuated l -NAME-induced increases in perfusion pressure (P</= 0.05, regression analysis, ANOVA). Low oxygen perfusion was associated with an increase in CRH secretion into the maternal but not fetal circulation. CRH release into either the maternal or fetal circulations of abnormal placentae were not significantly different from normal controls. In conclusion CRH-induced vasodilatation of the fetal placental vasculature in vitro is inhibited during low oxygen perfusion. This effect may be related to reduced NO production. Reduced CRH induced vasodilation is associated with increased secretion of the CRH into the maternal but not fetal circulation.
Placenta 2000 Sep
PMID:Fetal placental vascular responses to corticotropin-releasing hormone in vitro. Effects of variation in oxygen tension. 1098 75

A role for angiogenic growth factors in trophoblast invasion has been postulated. Directional motility (chemotaxis) is an important function of trophoblast cells. We have previously shown that vascular endothelial growth factor (VEGF) increases the random movement of trophoblast cells although placental growth factor (PlGF) has no effect. Heparin inhibited this effect of VEGF. Motility of trophoblast cells has been proposed to be mediated by a nitric oxide (NO) pathway. We hypothesized that VEGF but not PlGF would be chemotactic for trophoblast cells. Chemotaxis of a first trimester extravillous trophoblast cell line, SGHPL-4, and primary isolates of first trimester and term trophoblast cells was measured using a Boyden chamber. Initial experiments to optimize the time of the experiment and identify a positive control were performed. Subsequent experiments ran for 20 h, used 0.5 per cent FBS or 10 ng/ml PDGF as negative and positive controls and were performed in triplicate. VEGF (1, 10 and 100 ng/ml+/-1 microg/ml heparin or +/-100 microM L-NAME) and PlGF (1, 10, 100 ng/ml) were tested. The chamber was placed in a 5 per cent CO(2) in air, 37 degrees C incubator. The number of cells in the lower chamber were counted. There was a dose dependent increase in chemotactic motility of the SGHPL-4 cell line and term trophoblast cells in response to VEGF. PlGF had no effect on the movement of the first trimester trophoblast cell line but did increase the motility of the term trophoblast cells in a dose dependent manner. Heparin increased the cellular motility of both cell types alone. It also further enhanced the chemoactivity of VEGF on the term trophoblast cells but not the cell line. L-NAME did not affect the VEGF-stimulated motility of the first trimester cell line. However, in the term trophoblast cells L-NAME increased the directional cellular motility in the absence of, or in the presence of low concentrations of VEGF. In conclusion, the first trimester and term trophoblast cells appeared to respond differently to the various factors tested in the present study that may reflect differential cellular function as gestation progresses.
Placenta 2003 May
PMID:Vascular endothelial growth factor is a chemoattractant for trophoblast cells. 1274 32

Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone in health and disease. The present study addresses the contribution of NO to the baseline vascular tone in the fetal placental circulation of type 1 diabetic women. To this end, we performed ex-vivo dual perfusions of isolated cotyledons from seven women with type 1 diabetes mellitus and 24 healthy women. The fetal arterial pressure was considered to be a measure of fetal vascular resistance. The contribution of NO to the baseline vascular tone of the fetal placental circulation was quantified by addition of the NO-synthase inhibitor N(G)-nitro-arginine-methylester (L-NAME). Apart from the diabetic state, we studied the influence of exogenous insulin on the response to L-NAME. Mean (+/-SEM) baseline fetal arterial pressure was higher in diabetes (25.7+/-3.4 mm Hg vs 18.0+/-1.7 mm Hg, P<0.05). Maximum perfusion pressure after L-NAME was 87.9+/-7.1 mm Hg in diabetes vs 58.9+/-4.5 mm Hg in controls (P<0.01). The net L-NAME-induced increase in fetal arterial pressure was higher in diabetes (62.2+/-9.1 mm Hg vs 40.9+/-3.5 mm Hg, P<0.05). Although insulin induced a shift to the left of the L-NAME-curve, the net L-NAME-induced increase in fetal arterial pressure was not affected. We conclude that diabetes is associated with an increased baseline vascular tone of the fetal placental vascular bed. This can not be explained by attenuated NO-mediated effects. In contrast, the activity of the NO-pathway seems to be increased in diabetes. The latter observation seems not to be caused by high insulin levels.
Placenta 2003 Nov
PMID:Nitric oxide-mediated vascular tone in the fetal placental circulation of patients with type 1 diabetes mellitus. 1458 Mar 80

Nitric oxide (NO) is believed to play pivotal roles in embryo implantation. The purpose of this study was to investigate the effect of NO on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as the mechanism of NO during mouse implantation. Nitric oxide synthase (NOS) inhibitor, L-NAME was administered with or without sodium nitroprusside (SNP), NO donor, into one uterine horn on day 3 of pregnancy, and the contralateral uterine horn served as the control. We collected the uteri on days 5, 6, and 7 of pregnancy and examined the mRNA expression of MMP-2, -9, and TIMP-1, -2, -3, as well as the activities of MMP-2 and -9 by using in situ hybridization and gelatin zymography, respectively. The results showed that, compared with the control, the expression of MMP-2 and -9 mRNAs was decreased in L-NAME-treated uteri during peri-implantation. Treatment of mice with L-NAME had slight effect on the expression of TIMP-1 mRNA on day 5 of pregnancy, and no effect on TIMP-2 mRNA expression during peri-implantation. However, the expression of TIMP-3 mRNA was increased. The gelatin zymography results indicated that the activity of MMP-9 was decreased during peri-implantation, but the activity of MMP-2 did not change significantly in these time points examined. The L-NAME-mediated effect on MMPs and TIMPs were significantly reversed when SNP was co-administered with L-NAME. These data suggest that inhibition of NO production regulates the gene expression of MMP-2, -9, and TIMP-3, together with the activity of MMP-9 during peri-implantation, which may have serious consequence on embryo implantation.
Placenta 2004 Apr
PMID:Regulation of matrix metalloproteinases (MMPS) and their inhibitors (TIMPS) during mouse peri-implantation: role of nitric oxide. 1502 15

Oxidative stress plays an important role in the development of pre-eclampsia. Recently, the superoxide producing enzyme NAD(P)H oxidase was shown to be present in placental trophoblast. In this pilot-study we investigated the NAD(P)H oxidase associated superoxide production as modulator of placental oxidative stress in normotensive pregnancy (n = 19; gestational age 38(+6)+/-0(+1)weeks(+days)) and pre-eclampsia (n = 15; gestational age 34(+3)+/-1(+5)weeks(+days)) using a lucigenin assay. Specificity of superoxide generation by NAD(P)H oxidase was assessed using the inhibitors L-NAME, rotenone, allopurinol, DPI and TIRON. Superoxide production was measurable in all placenta tissues and was inhibited by DPI and TIRON. No significant differences for total superoxide production (O2*total), maximal superoxide production (O2*max), or the rate of superoxide production were found between normotensive and pre-eclamptic women. However, women with early onset of disease had a higher O2*total as compared to those with a late onset disease. We conclude that human placenta contains a functional NAD(P)H oxidase that is highly active, which could be an important source of superoxide during pregnancy and pre-eclampsia. These data justify more detailed investigation of the role of NAD(P)H oxidase and placental oxidative stress in complicated pregnancies.
Placenta 2004 Apr
PMID:NAD(P)H oxidase associated superoxide production in human placenta from normotensive and pre-eclamptic women. 1503 13

Vascular endothelial-cadherin (VE-cadherin), a calcium-dependent homotypic adhesion molecule, contributes to endothelial assembly and VEGF-mediated survival during angiogenesis. In human term placentas, villous vessels and extravillous cytotrophoblasts express VE-cadherin. Therefore, the purpose of this study was to examine if VEGF modulated placental development by increasing the expression of VE-cadherin in rat placentas. Placental tissues from rats on gestation days 14 (G14), 18 (G18) and 21 (G21) were used. Western blot analysis and immunohistochemistry were performed to detect the protein abundance and the distribution of VE-cadherin. A nitric oxide analyzer was used to measure the released nitric oxide (NO) from placental explant culture. With the progression of pregnancy, the abundance of VE-cadherin and the intensity of the immunoreactive staining for VE-cadherin in endovascular trophoblasts and labyrinth trophoblasts were decreased. In explant culture, VEGF (0.01-1.0 ng/ml) increased the protein abundance of VE-cadherin. SNP (an NO donor) or L-arginine (substrate for eNOS) induced the expression of VE-cadherin with the increase of NO production. L-NAME (a NOS inhibitor) reduced the VEGF-increased expression and L-arginine reversed the inhibitory effect of L-NAME. In conclusion, VEGF plays an important role in placental development by the induction of VE-cadherin in trophoblasts, which, in part, maintains the survival of labyrinth trophoblast in rat placentas.
Placenta
PMID:Induction of VE-cadherin in rat placental trophoblasts by VEGF through a NO-dependent pathway. 1570 25

The vasoactive mediators nitric oxide and endothelin are both produced in and active in the uterine and placental vasculature. Inhibition of nitric oxide synthase (NOS) results in fetal growth restriction. Endothelin (ET-1) is upregulated in the setting of NOS inhibition. Our purpose was to determine the impact of ET-1 on uterine and placental perfusion in the pregnant rat treated with a NOS inhibitor. Timed-pregnant Sprague-Dawley rats were treated with L-NAME (2.5 mg/kg/h), with and without A-127722 (10 mg/kg/day), or their respective vehicles, for 1, 4, or 7 days beginning on day 14 of gestation. Blood flow to various organs was determined by microsphere infusion. Maternal and fetal plasma nitrate/nitrite (NOx) was determined by fluorometric assay. Uterine and placental perfusion was significantly decreased by NOS inhibition and was restored to normal by ETA antagonism at 1 and 4 days of infusion but not at 7 days. Maternal plasma NOx, but not fetal plasma NOx, was significantly decreased by NOS inhibition alone. ETA antagonism in combination with NOS inhibition significantly lowered fetal plasma NOx. These results indicate that ET-1 is an important regulator of uterine and placental perfusion in the NOS inhibition model of fetal growth restriction. Our results also suggest that maternal administration of L-NAME does not result in significant transport of L-NAME across the placenta, but that addition of an ETA antagonist results in increased placental perfusion, allowing L-NAME greater access to the fetal compartment.
Placenta
PMID:Endothelin and the regulation of uteroplacental perfusion in nitric oxide synthase inhibition-induced fetal growth restriction. 1570 26

Using cytokeratin-7-positive trophoblast cells (hTr) isolated from human term placentas and the choriocarcinoma cell lines (hCC) BeWo, Jeg-3 and JAr, the expression of genes involved in the hepatobiliary excretion of cholephilic compounds was investigated by RT-PCR/sequencing followed by measurement of the absolute abundance of mRNA by real-time RT-PCR. Although mRNA of BSEP was detectable and its expression confirmed by Western blotting, its very low expression (higher in hTr than in whole placenta and hCC) did not permit its detection by immunohistochemistry. In hTr, the expression was high for OATP-B/2B1, OATP-8/1B3, MRP1, MRP3, BCRP, FIC1, RARalpha, FXR and SHP, low for OSTalpha, MRP2, MRP4, MRP8, MDR1, CAR and SXR, very low for OATP-A/1A2 and MDR3, and not detectable for OATP-C/1B1, HNF1alpha and HNF4. Expression patterns in hCC mimicked those in hTr, although some important cell line-specific differences were found. The functionality of transporters expressed in hCC was confirmed by their ability to take up and export estradiol 17beta-d-glucuronide in a self-inhibitable and temperature-sensitive manner. In conclusion, several transporters, export pumps, and nuclear receptors involved in the liver excretory function may play a similar role in the placenta, whose specific aspects can be studied by selectively using BeWo, Jeg-3 or JAr cells.
Placenta
PMID:Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. 1671 28


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