Original Articles
Maternal cigarette smoking increases F2-isoprostanes and reduces prostacyclin and nitric oxide in umbilical vessels

https://doi.org/10.1016/S0090-6980(99)00011-8Get rights and content

Abstract

The objective of this study was to evaluate the influence of smoking on F2-isoprostanes, prostacylin and nitric oxide in human umbilical vessels. Umbilical cords from 13 babies of smoking mothers and from 28 babies of non-smoking mothers were examined for levels of F2-isoprostanes, prostacyclin, l-arginine, and l-citrulline. Forty-one umbilical arteries and eleven umbilical veins were analyzed. Statistical analysis of data was done using modified t-test. Cigarette smoking increased F2-isoprostane levels and reduced the generation of prostacyclin, l-arginine and l-citrulline comparably in umbilical arteries and veins. Notably, in umbilical cords of babies of non-smoking mothers the F2-isoprostane level was significantly higher in arteries. Cigarette smoking correlates with a direct vasoconstrictive effect. We suggest that smoking might enhance the vasoconstrictory capacity in umbilical arteries by increased F2-isoprostanes and by a simultaneous decrease in the production of the vasodilatory compounds, prostacyclin, and nitric oxide.

Introduction

Smoking during pregnancy causes reduced birth weight and an increase in perinatal mortality and morbidity [1]. Prostaglandins (PG) have shown to be of great importance for the regulation of fetal and umbilico–placental circulation [2]. Prostacyclin (PGI2) is the most potent vasodilating agent of this group of substances [3], [4]. It is quickly metabolizes to its stable derivative 6-oxo-PGF. Smoking damages the endothelial surface layer [5]. As vascular endothelium has been shown to be the major site of PGI2-formation [6], this might explain the reduced PGI2-generation reported in umbilical arteries of babies born to smoking mothers [7], [8].

PGI2 and nitric oxide (NO) act synergistically when released from endothelial cells [9]. They are known to down-regulate vascular tone. Recently, we found that not only PGI2, but also NO is reduced in umbilical arteries from smoking mothers [10]. Cigarette smoking has been claimed to be associated with oxidative damage by free radicals [11]. The recently discovered F2-isoprostane 8-epi-PGF proved to be a potent in vivo marker of oxidation injury [12], [13]. F2-Isoprostanes are produced independently from the cyclooxygenase pathway in humans by peroxidation of arachidonic acid, catalyzed by free oxygen radicals. As we know that smoking increases the generation of F2-isoprostanes in plasma and urine [14], our hypothesis was that F2-isoprostanes could be involved in the adverse effects produced by smoking in pregnancy. Considering earlier investigations that smoking reduces prostacyclin and nitric oxide [7], [8], [10], this analysis was undertaken to explore the influence of smoking on the generation of F2-isoprostanes in umbilical vessels.

Section snippets

Study population

Forty-one healthy pregnant women who had an uneventful course of pregnancy were enrolled in this study after giving informed consent. They were divided into 13 smokers (at least 10 cigarettes per day during pregnancy) and 28 non-smokers. Ex-smokers were also excluded. All were giving birth after the 36th week of gestation. Drug intake during the previous 2 weeks was restricted. There were no significant differences in parity, maternal weight, blood pressure, or plasma lipids, way of delivery,

F2-isoprostanes

8-epi-PGF-values were significantly higher in umbilical cords of babies of smoking mothers (Table 2). There, the values of 8-epi-PGF in umbilical arteries (392.4 ± 104.8) and veins (399.6 ± 94.4) were quite similar. In non-smoking mothers, however, higher values of 8-epi-PGF were found in umbilical arteries (181.3 ± 31.3) versus umbilical veins (147.0 ± 25.6; p = 0.017).

PGI2-production

PGI2-levels were significantly lower in umbilical cords of babies of smoking mothers. PGI2-levels in arteries and veins

Discussion

A close relationship between fetal growth and blood flow in umbilical vessels is obvious. Besides, the direct vasoconstrictive effect of nicotine is known to exert a negative influence on vascular perfusion via different pathways, thereby causing impaired fetal nutrition and increased perinatal mortality [7], [8], [10].

Morrow et al. [14] first reported that smoking cigarettes increases circulating products of lipid peroxidation (F2-isoprostanes). They examined plasma levels of free F2

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Dr. Anthony Oguogho was a stipendiate from the Edo State University, Faculty of Basic Medical Sciences, Ekpoma, Nigeria, supported by a grant of the Austrian Academic Exchange Division.

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