Nitric oxide concentrations are increased in the fetoplacental circulation in preeclampsia

Lyall, Fiona; Young, Anne; Greer, Ian A.

doi:10.1016/0002-9378(95)90328-3

Cited by 122 publications

(57 citation statements)

References 19 publications

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“…There are reports that the NO metabolites, nitrite and nitrate, are increased in the cord blood of infants of preeclamptic women. 34 In addition, we reported that exposure of endothelial cells to plasma from cord blood of infants of preeclamptic mothers increases NO production. 35 These data provide overall support for a local increase in reactive oxygen species generation in the placental beds of preeclamptic women.…”

Section: Discussionmentioning

confidence: 97%

Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia

Many

Hubel

Fisher

et al. 2000

The American Journal of Pathology

247

150

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In preeclampsia, poor placental perfusion may result in maternal endothelial dysfunction, but the pathways involved are largely unknown. Candidate placental mediators include products of oxidative stress released into the maternal circulation. Xanthine oxidase has been implicated in postischemic-reperfusion injury via the generation of superoxide anion radicals (superoxide; O 2 .؊ ) and hydrogen peroxide. We examined placentas and placental bed curettings and/or biopsies from preeclamptic control pregnant women to test the hypothesis that xanthine oxidase is a mediator of oxidative stress in placentas from women with preeclampsia. The expression of xanthine dehydrogenase/xanthine oxidase holoenzyme and the activity of xanthine oxidase, the isoform known to generate reactive oxygen species, were increased in a subpopulation of cytotrophoblasts of preeclamptic women. Additionally, the expression of superoxide dismutase, which would scavenge superoxide produced by xanthine oxidase, was reduced in the same cells. Preeclampsia, a pregnancy-specific disorder, is the leading cause of maternal mortality in the Western world and increases perinatal mortality fivefold. The clinical diagnosis is based on the new onset of hypertension and the appearance of proteinuria and edema during pregnancy. It is evident, however, that these findings are a small component of a multisystemic disease that reduces perfusion to virtually all of the organs in the body. 1 The hypothesis has been advanced that much of the disease could be explained by alterations in the function of vascular endothelium. Increasing data support this hypothesis. 2 The more complete hypothesis posits that the placenta, likely in response to reduced perfusion, produces a circulating factor(s) that alters endothelial cell function. 2 Among the candidate molecules are products resulting from oxidative stress. 3 Oxidative stress, the result of freeradical generation in excess of protective mechanisms, is suggested as an important component of other disorders that affect endothelial function, including diabetes and atherosclerosis. 4,5 Evidence for oxidative stress in preeclampsia includes elevated lipid hydroperoxides or their metabolites and reduced plasma antioxidant activity. 3,6 -8 Xanthine oxidase, which metabolizes xanthine and hypoxanthine to uric acid with production of superoxide and hydrogen peroxide, is an integral mediator of reactive oxygen species generation in many settings. Usually, this enzyme is present as the holoenzyme xanthine dehydrogenase/xanthine oxidase (XDH/XO). The dehydrogenase isoform (XDH) converts purines to uric acid with reducton of nicotinamide-adenine dinucleotide (NAD) to reduced NAD (NADH). With hypoxia and in response to several cytokines, XDH/XO synthesis increases, and the conversion of the enzyme to the XO form is enhanced. 9 Reduced organ perfusion and subsequent reperfusion are proposed to result in increased XO during reduced flow and in subsequent formation of reactive oxygen species with reperfusion. The inadequate pla...

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Section: Discussionmentioning

confidence: 97%

Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia

Many

Hubel

Fisher

et al. 2000

The American Journal of Pathology

247

150

View full text Add to dashboard Cite

show abstract

“…The pharmacological actions of nitric oxide in the human fetal placental vasculature in vitro have been studied 23 . Lyall et al 20 reported that a higher concentration of total combined serum nitrite and nitrate was present in umbilical venous serum from pre-eclampsia. Higher plasma total nitrites were shown in IUGR 21 .…”

Section: Discussionmentioning

confidence: 99%

Gene expression of nitric oxide synthase by human umbilical vein endothelial cells: the effect of fetal plasma from pregnancy with umbilical placental vascular disease

Wang¹

2003

BJOG: An International Journal of Obstetrics and Gynaecology

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Objective To determine whether endothelial cell injury would be produced by factor(s) released into the fetal circulation, manifested by altered messenger RNA expression of nitric oxide synthase. Design Case -control study.Setting University teaching hospital.Samples Fetal plasma was collected from 34 normal pregnancies, 44 pregnancies with umbilical placental vascular disease identified by an abnormal umbilical Doppler and 11 pregnancies with maternal pre-eclampsia but with normal umbilical Doppler studies. Methods Aliquots from a common culture of human umbilical vein endothelial cells (HUVECs) were incubated with fetal plasma from the members of the three patient groups. The total RNA was extracted from the endothelial cells and mRNA for nitric oxide synthase was measured by reverse transcription and semi-quantitative polymerase chain reaction (RT-PCR). This was standardised by comparison of the amplified inducible nitric oxide synthase (iNOS) or endothelial constitutive nitric oxide synthase (ecNOS) to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Main outcome measure Endothelial cell gene expression of iNOS and ecNOS.Results The mRNA expression of iNOS and ecNOS were significantly higher ( P < 0.05) in HUVECs stimulated by fetal plasma from pregnancies with umbilical placental vascular disease [iNOS 1.12 (0.16); ecNOS 1.78 (0.18)] when compared with normal pregnancies [iNOS 0.56 (0.06); ecNOS 1.06 (0.10)]. In the maternal pre-eclampsia group, the NOS expression [iNOS 0.76 (0.11); ecNOS 1.39 (0.26)] did not differ from normal pregnancy. In the vascular disease group, there was no difference in NOS expression between the subgroups with and without maternal pre-eclampsia. Conclusions Our study demonstrates that umbilical placental vascular disease is associated with a factor(s) in fetal plasma that produces an increase in the expression of iNOS and ecNOS mRNA by endothelial cells. Our findings raise the possibility that the release of factors causing an up-regulation of iNOS and ecNOS in the endothelium in the fetal placenta may occur as part of an inflammatory response of the vascular endothelium to injury.

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“…Experiments conducted in hypertensive animals have shown a similar diversity of findings, with NO generation reported to be normal, decreased, or enhanced. [21][22][23][24][25][26][27][28][29] Studies with reduced NO basal production in patients with essential hypertension were reported. 30,31) The data were largely attributed to the reduced bio-activity of NO.…”

Section: Discussionmentioning

confidence: 99%