Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth‐retarded and pre‐eclamptic pregnancies

Rutherford, Richard A.D.; McCarthy, Andrew L.; Sullivan, Mark; Elder, M. G.; Polak, Julia M.; Wharton, John

doi:10.1111/j.1476-5381.1995.tb15111.x

Cited by 71 publications

(38 citation statements)

References 68 publications

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“…This observation suggests that elevated maternal ADMA (raised in DDAH1 (wt/del) heterozygotes (Leiper et al, 2007)) may negatively impact embryonic viability post-implantation. Consistent with this suggestion, elevated plasma ADMA levels have been reported in human pre-eclampsia (Savvidou et al, 2003) and intrauterine growth retardation (Rutherford et al, 1995). …”

Section: Discussionsupporting

confidence: 69%

A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development

Breckenridge¹,

Kelly²,

Nandi³

et al. 2010

Int. J. Dev. Biol.

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Nitric oxide has been linked to a number of embryonic processes, yet the role of nitric oxide signalling in development remains largely unknown. Dimethylarginine Dimethylaminohydrolase 1 and 2 (DDAH1/2) catalyse the breakdown of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide production, and may also have nitric oxide-independent functions. We have generated transgenic mice targeting the DDAH1 and DDAH2 loci. Here we report that homozygous DDAH1 null embryos are generated at low frequency, and do not progress through embryonic development. During normal development DDAH1 RNA is expressed in the left ventricle, cardiac outflow tract and developing vasculature. In contrast, DDAH2 homozygous null mice are viable and fertile, with a normal lifespan. DDAH2 expression is seen in the developing left ventricle and cardiac outflow tract, and additionally in the peripheral nervous system. Both DDAH1 and 2 are expressed in the developing limb buds in patterns overlapping areas with high nitric oxide synthase activity. These expression patterns implicate DDAH1 and DDAH2 in embryonic development, possibly through specific effects on nitric oxide pathways.

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Section: Discussionsupporting

confidence: 69%

A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development

Breckenridge¹,

Kelly²,

Nandi³

et al. 2010

Int. J. Dev. Biol.

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“…Previous studies have reported reduction in NOS activity in the umbilical artery endothelium, 27 and fetoplacental NO synthesis is decreased during pregnancies complicated by fetal growth restriction. 28,29 On the other hand, other authors have found that concentrations of plasma nitrates and nitrites are higher in the fetal circulation of growth-restriction pregnancies in comparison with normal pregnancies.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine and Nitric Oxide Are Related to Blood Pressure and Vascular Function in Small-for-Gestational-Age Children

et al. 2007

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Abstract-Leptin, homocysteine (Hcy), and C-reactive protein are risk factors potentially useful in predicting future cardiac events. These plasma biomarkers may participate in the regulation of cardiovascular function through an NO-dependent mechanism. Our purpose was to investigate whether alterations in C-reactive protein, Hcy, leptin, and NO are present in small-for-gestational-age children and to determine whether the levels of these plasma biomarkers are associated with birth weight, vascular function, and blood pressure. Concentrations of leptin, Hcy, C-reactive protein, and NO were measured in 69 children (36 boys and 33 girls; ages 8 to 13 years). Leptin (means difference: 1.4 ng/mL; 95% CI: 0.4 to 2.4) and Hcy (means difference: 0.9 mol/L; 95% CI: 0.3 to 1.5) levels were significantly elevated in children born small for gestational age compared with those with appropriate birth weight. Nevertheless, NO (means difference: 342.9 mol; 95% CI: 124.2 to 561.6) concentration was significantly reduced in small birth weight children, and the levels of C-reactive protein remained unchanged. There was a significant association between the circulating levels of both NO and Hcy with vascular function, as well as with blood pressure levels, in our population. Because both Hcy and NO are associated with a risk of cardiovascular disease, it is possible that part of the association of low birth weight with elevated risk for vascular and metabolic disease in later life is mediated by perturbation in pathways for these biomarkers.

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“…For instance, women with intrauterine growth-restricted pregnancies have a lower NO-dependent flow-mediated dilation and a higher plasma level of asymmetric dimethylarginine (ADMA), an inhibitor of eNOS that competes with L-arginine, than women with normal pregnancies. 15 In addition, a lower eNOS expression in the umbilical artery 16 and a lower eNOS activity in placental villus tissue 17 are found in intrauterine growthrestricted compared with normal pregnancies. In an earlier study, we found a smaller fetal outcome and lower eNOS activity and concentration in fetal umbilical veins exposed to maternal smoking compared with those of lifelong nonsmoking mothers.…”

Section: Clinical Perspective P 864mentioning

confidence: 99%

Smoking Cessation Early in Pregnancy and Birth Weight, Length, Head Circumference, and Endothelial Nitric Oxide Synthase Activity in Umbilical and Chorionic Vessels

Andersen

Simonsen²,

Uldbjerg³

et al. 2009

Circulation

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Background-Reduced production of the vasodilator nitric oxide (NO) in fetal vessels in pregnant smokers may lower the blood flow to the fetus and result in lower birth weight, length, and head circumference. The present study measured endothelial NO synthase (eNOS) activity in fetal umbilical and chorionic vessels from nonsmokers, smokers, and ex-smokers and related the findings to the fetal outcome. Methods and Results-Of 266 healthy, singleton pregnancies, 182 women were nonsmokers, 43 were smokers, and 41 stopped smoking early in pregnancy. eNOS activity and concentration were quantified in endothelial cells of the fetal vessels. Cotinine, lipid profiles, estradiol, L-arginine, and dimethylarginines that may affect NO production were determined in maternal and fetal blood. Serum cotinine verified self-reported smoking. Newborns of smokers had a lower weight (PՅ0.001) and a smaller head circumference (PՅ0.041) and were shorter (PՅ0.001) than newborns of nonsmokers and ex-smokers. eNOS activity in umbilical veins of smokers was 36% lower (PϽ0.001), eNOS concentration was 47% lower (PϽ0.001), and the fetal plasma level of high-density lipoprotein was 18% lower (PϽ0.001) than those of nonsmokers, whereas the same levels were found in umbilical veins from ex-smokers and nonsmokers. The same patterns in eNOS activity and concentration were found in umbilical arteries and chorionic vessels. Fetal plasma levels of estradiol, L-arginine, dimethylarginines, total cholesterol, and triglycerides were similar for nonsmokers, smokers, and ex-smokers. Conclusions-The findings suggest that maternal smoking reduces eNOS activity in the fetal vascular bed, contributing to retarded fetal growth caused by the reduction of vasodilatory capacity, and suggest that smoking cessation early in pregnancy prevents these effects in newborns. (Circulation. 2009;119:857-864.)

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Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth‐retarded and pre‐eclamptic pregnancies

Abstract: 1 It has been suggested that a deficiency of nitric oxide (NO) may explain many of the pathophysiological features of pre-eclampsia (PE) and intra-uterine (foetal) growth retardation (IUGR

Cited by 71 publications

References 68 publications

A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development

A role for Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) in mammalian development

Homocysteine and Nitric Oxide Are Related to Blood Pressure and Vascular Function in Small-for-Gestational-Age Children

Smoking Cessation Early in Pregnancy and Birth Weight, Length, Head Circumference, and Endothelial Nitric Oxide Synthase Activity in Umbilical and Chorionic Vessels

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