Placental nitric oxide synthase (NOS) activity and nitric oxide (NO) production in normal pregnancy, pre-eclampsia and eclampsia

Shaamash, Ayman H.; Elsonosy, E.D.; Zakhari, M.M.; Radwan, Sh.H.; Eldien, Heba M. Saad

doi:10.1016/s0020-7292(00)00314-3

Cited by 47 publications

(34 citation statements)

References 24 publications

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“…This finding is in correlation with the studies that previously proposed increased NO levels as a result of insufficient compensatory mechanisms to supress vasoconstriction (Shaamash et al, 2001). The subclinic renal dysfunction may cause insufficient clearence of NO metabolites namely nitrate and nitrite.…”

Section: Discussionsupporting

confidence: 90%

Comparison of maternal serum and umbilical cord concentrations of nitric oxide and asymmetric-dimethyl-arginine in pre-eclamptic and uncomplicated pregnancies

Albayrak¹,

Öncül²,

Uludağ³

et al. 2013

jecm

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Article HistoryReceived 02 / 12 / 2012 Accepted 04 / 05 / 2013The aim of this study was to compare maternal serum and umbilical cord levels of asymmetric-dimethyl-arginine (ADMA) and nitric oxide (NO) in pre-eclamptic and non-pre-eclamptic women and the possible effects of ADMA and NO on fetal outcome. Mean umbilical cord and maternal serum NO and ADMA levels of 29 women with preeclampsia (PE) and 24 randomly selected healthy pregnant women were compared. Maternal venous blood samples were collected before delivery and umbilical cord venous blood samples were obtained after delivery. Birth weight, apgar score, cord blood pH, duration of stay in the neonatal intensive care unit (NICU), and maternal and neonatal complications were recorded. Umbilical cord ADMA and maternal NO levels were significantly higher in women with pre-eclampsia compared to women without pre-eclampsia. There were no significant differences between means of maternal serum ADMA levels and cord blood NO levels in women with and without pre-eclampsia. Maternal and cord serum NO and ADMA levels in the pre-eclampsia group did not show a significant correlation with cord blood pH, umbilical artery pulsatility index (PI). In conclusion, umbilical cord ADMA and maternal NO levels were significantly higher in women with pre-eclampsia compared to women without pre-eclampsia.

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Section: Discussionsupporting

confidence: 90%

Comparison of maternal serum and umbilical cord concentrations of nitric oxide and asymmetric-dimethyl-arginine in pre-eclamptic and uncomplicated pregnancies

Albayrak¹,

Öncül²,

Uludağ³

et al. 2013

jecm

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“…42 This would imply that eNOS in the hypoxic placenta may contribute to dysregulated oxidative stress. In that case, increased placental eNOS expression observed in some preeclamptic human pregnancies (eg, References 43 and 44) instead of playing a compensatory role as previously thought 43 may actually contribute to the maternal disease. It is interesting that elimination of eNOS protein appears to block the progression from stage 1 to stage 2 of preeclampsia (current study), whereas blocking the enzymatic activity of eNOS by N Gnitro-L-arginine methyl ester does not.…”

Section: Perspectivesmentioning

confidence: 77%

Endothelial Nitric Oxide Synthase Deficiency Reduces Uterine Blood Flow, Spiral Artery Elongation, and Placental Oxygenation in Pregnant Mice

et al. 2012

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Abstract-Preeclampsia is associated with impaired uteroplacental adaptations during pregnancy and abnormalities in the endothelial NO synthase (eNOS)-NO pathway, but whether eNOS deficiency plays a causal role is unknown. Thus, the objective of the current study was to determine the role of eNOS in the mother and/or conceptus in uteroplacental changes during pregnancy using eNOS knockout mice. We quantified uterine artery blood flow using microultrasound, visualized the uteroplacental vasculature using vascular corrosion casts, and used pimonidazole and hypoxia-inducible factor 1␣ immunohistochemistry as markers of hypoxia in the placentas of eNOS knockout mice versus the background strain, C57Bl/6J (wild type). We found that increases in uteroplacental blood flow, uterine artery diameter, and spiral artery length were reduced, and markers of placental hypoxia in the junctional zone were elevated in late gestation in eNOS knockout mice. Both maternal and conceptus genotypes contributed to changes in uterine artery diameter and flow. Despite placental hypoxia, placental soluble fms-like tyrosine kinase 1 and tumor necrosis factor-␣ mRNA, and in maternal plasma, soluble fms-like tyrosine kinase 1 were not elevated in eNOS knockout mice. Thus, our results show that both eNOS in the mother and the conceptus contribute to uteroplacental vascular changes and increased uterine arterial blood flow in normal pregnancy. Key Words: preeclampsia/pregnancy Ⅲ blood flow regulation Ⅲ NO Ⅲ hypoxia Ⅲ placenta Ⅲ endothelial NO synthase T he maternal cardiovascular system undergoes structural and functional changes to accommodate the increased circulatory requirements of the growing fetus. Nowhere is this more profound than in the uteroplacental vasculature, where a marked increase in uteroplacental blood flow is achieved by a large reduction in vascular resistance 1,2 and pronounced enlargement and structural reorganization of the uterine and spiral arteries.3 Failure to make or to sustain these changes may result in preeclampsia, one of the most common and serious complications of human pregnancy.The mechanisms mediating uteroplacental changes during pregnancy are not fully understood. However, the L-arginine-NO pathway appears to play a central role in both normal pregnancy and in preeclampsia. 4 In preeclampsia in humans, diverse elements of the l-arginine-NO signaling pathway may be abnormal, including reduced l-arginine substrate or cofactor availability, reduced endothelial NO synthase (eNOS) enzyme activity attributed to gene polymorphisms, or elevated levels of asymmetrical dimethylarginine. 4 In pregnant rats 5 and mice, 6 NO synthase inhibition with N G -nitro-L-arginine methyl ester induces preeclamptic signs.Despite considerable evidence implicating eNOS in preeclampsia, eNOS knockout (KO) mice do not develop the hallmark signs, gestational hypertension 7-9 or proteinuria. 9Indeed, arterial pressure in eNOS KO mice decreases during pregnancy to become similar to that of pregnant wild-type controls. 7-9 Nevertheless, t...

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“…Binding of VEGF to its functional receptors will help it to induce NO and vasodilatory prostacyclins in endothelial cells, leading to decreased vascular tone and BP. 36,37 In this case, VEGF works in association with NO to maintain normal structure and function of the glomerular basement membrane, 40 stimulate glomerular repair, and inhibit proteinuria. 41 This pathway could explain the amelioration of proteinuria and hypertension in the PRE þ MgSO 4 group in the current study.…”

Section: Discussionmentioning

confidence: 99%

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis

Korish

2012

Hypertens Res

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A disturbed balance between angiogenic and antiangiogenic growth factors is a highly accepted mechanism in the pathogenesis of pregnancy-induced hypertension and proteinuria, which is clinically known as preeclampsia (PE). We investigated the effect of magnesium sulfate (MgSO 4 ) therapy on vascular endothelial growth factor (VEGF), placental growth factor (PlGF), nitric oxide (NO) metabolites, soluble fm-like tyrosine kinase-1 (sFlt-1) and endoglin levels in PE rats and the effect of this treatment on the feto-maternal outcome. The PE group showed hypertension, proteinuria and decreased number and weight of live pups relative to the control group. This result was associated with increased sFlt-1, VEGF receptor-2 (VEGFR-2), VEGFR-3 and endoglin levels but decreased NO metabolites. MgSO 4 therapy ameliorated systolic hypertension and proteinuria and decreased sFlt-1, VEGFR-2, VEGFR-3 and endoglin levels but increased NO metabolites in the treated group. Physiological and biochemical changes and improved pup weight and viability were observed in the treated group. The vasodilator action of MgSO 4 and increased NO production are expected to increase placental blood flow and help fetal nutrition and development. Relief of placental ischemia decreases the production of antiangiogenic growth factors and restores the bioavailability of angiogenic factors (PlGF and VEGF). These changes resulted in better fetal outcome and an improved clinical picture of PE. These findings are promising and encourage further study of the mechanism of action of MgSO 4 to support its widespread use in the prevention and management of the etiopathological changes underlying the vast majority of the manifestations and complications of PE.

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Placental nitric oxide synthase (NOS) activity and nitric oxide (NO) production in normal pregnancy, pre-eclampsia and eclampsia

Cited by 47 publications

References 24 publications

Comparison of maternal serum and umbilical cord concentrations of nitric oxide and asymmetric-dimethyl-arginine in pre-eclamptic and uncomplicated pregnancies

Comparison of maternal serum and umbilical cord concentrations of nitric oxide and asymmetric-dimethyl-arginine in pre-eclamptic and uncomplicated pregnancies

Endothelial Nitric Oxide Synthase Deficiency Reduces Uterine Blood Flow, Spiral Artery Elongation, and Placental Oxygenation in Pregnant Mice

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis

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