Systemic and fetal–maternal nitric oxide synthesis in normal pregnancy and pre‐eclampsia

Abstract

Objective To investigate systemic and fetal‐placental nitric oxide synthesis by biochemical and molecular biology means in normal human pregnancy and pre‐eclampsia. Design and participants Three groups of women were studied healthy pregnant women (n= 8), pregnant women with pre‐eclampsia (n= 8), and age‐matched nonpregnant controls (n= 8). Pre‐eclamptic patients were treated with nifedipine (30–60 mg/day) for severe hypertension. Systemic nitric oxide synthesis was assessed in normal pregnant women at weeks 18–21, 29–32 and 38–39 and in pre‐eclamptic women on admission to the hospital (29–32 weeks, 30 on average), before the morning nifedipine administration. Nonpregnant women were studied twice at four‐week intervals as controls. The pattern of nitric oxide biosynthesis in fetal‐placental circulation was studied in normal and pre‐eclamptic women at the delivery. Setting Mario Negri Institute for Pharmacological Research, Bergamo, and the Division of Obstetrics and Gynaecology of the University of Brescia. Main outcome measures Plasma cGMP levels and platelet nitric oxide synthesis, assessed by measuring the conversion of [3H]L‐arginine to [3H]L‐citrulline as well as intracellular cGMP, were evaluated. Constitutive nitric oxide synthase (EC‐NOS) gene expression by Northern blot analysis and nitric oxide release by the conversion of [3H]L‐arginine to [3H]L‐citrulline were assessed in umbilical vein endothelial cells (HUVEC) and in placenta. Inducible nitric oxide synthase activity was also evaluated in HUVEC exposed to tumour necrosis factor α (TNFα) and in placenta homogenates incubated in calcium free medium. Results Plasma cGMP was higher in both normal pregnant and pre‐eclamptic women than in nonpregnant controls. In normal pregnancy cGMP rose as early as 18–21 weeks and remained elevated throughout pregnancy. [3H]L‐citrulline production and intracellular cGMP were comparable in platelets from all women. EC‐NOS gene expression and nitric oxide synthesis were identical in HUVEC and placenta from normal pregnant and pre‐eclamptic women. Conclusions Systemic levels of cGMP, the nitric oxide second messenger, are increased in normal pregnancy. Excessive nitric oxide production does not derive from platelets. Pre‐eclampsia is not associated with changes in fetal‐placental nitric oxide synthesis.

Effect of Smoking on Serum Concentrations of Total Homocysteine, Folate, Vitamin B₁₂, and Nitric Oxide in Pregnancy: A Preliminary Study

“…It is well known that normal pregnancy is associated with marked cardiovascular changes, and NO seems to be a major contributor to these physiological adaptive changes of normal pregnancy [14]. The concentration of total nitrites was previously found to be significantly increased in the maternal blood circulation during normal pregnancy as compared with healthy nonpregnant women [2,15]. Cigarette smoke is known to contain NO, and thus it is reasonable to assume that an elevation of NO and vasodilatation are transiently induced by cigarette smoking.…”

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

“…It may be a response to a decrease in fetal oxygenation. In another report, there was no difference in the plasma level of the nitric oxide second messenger cGMP in normal and preeclamptic pregnancies 26 . Although the findings concerning nitric oxide synthase activity in normal pregnancy and preeclampsia are sometimes conflicting, there is no evidence of a decreased nitric oxide production in pre-eclampsia 27 .…”

Nitric Oxide Production by Pre-Implantation Embryos in Response to Embryotoxic Factors

“…However, cases like intra-uterine growth retardation and pre-eclampsia [26,27] have been correlated to NO over-production. It thus appears that fine equilibrium reactions control NO production for exerting harmful or beneficial effects in many biological systems.…”