Original ArticlesMaternal cigarette smoking increases F2-isoprostanes and reduces prostacyclin and nitric oxide in umbilical vessels
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-PGF1α. 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-PGF2α 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-PGF2α-values were significantly higher in umbilical cords of babies of smoking mothers (Table 2). There, the values of 8-epi-PGF2α 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-PGF2α 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
References (23)
- et al.
Reduced umbilical artery prostacyclin formation in complicated pregnancies
Am J Obstet Gynecol
(1982) - et al.
Prostacyclin production by vascular smooth-muscle cells
Lancet
(1978) - et al.
Diminished prostacyclin formation in umbilical arteries of babies born to women who smoke
Lancet
(1981) - et al.
Umbilical arteries of babies born to cigarette smokers generate less prostacyclin and contain less arginine and citrulline compared with those of babies born to control subjects
Am J Obstet Gynecol
(1995) - et al.
The isoprostanes—current knowledge and directions for future research
Biochem Pharmacol
(1996) - et al.
Determination of aminoacids with 9-fluorenylmethyl chloroformate and reversed-phase high-performance liquid chromatography
J Chromatogr
(1983) Interaction of nicotine and prostaglandins in the cardiovascular system
Prostaglandins
(1982)- et al.
Reduced umbilical and placental prostacyclin in severe preeclampsia
Prostaglandins
(1980) - et al.
Decreased prostacyclin productiona characteristic of chronic placental insufficiency syndromes
Lancet
(1981) - et al.
Relation between umbilical prostacyclin production and blood-flow in the fetus
Lancet
(1983)
Evidence that prostacyclin deficiency is a specific feature in preeclampsia
Am J Obstet Gynecol
Cited by (41)
The effects of particulate ambient air pollution on the murine umbilical cord and its vessels: A quantitative morphological and immunohistochemical study
2012, Reproductive ToxicologyCitation Excerpt :There is a relationship between induction of DNA adducts and measures of oxidative stress in instances of exposure to PM and tobacco smoke [49,50]. Maternal cigarette smoking also increases isoprostanes in umbilical arteries and veins [51]. Apart from smoking, isoprostane levels in UC blood have been related to oxidative stress in the fetus during labour, preterm birth and PE [52].
F<inf>2</inf>-isoprostanes as an indicator and risk factor for coronary heart disease
2011, Free Radical Biology and MedicineNitric oxide-mediated blood flow regulation as affected by smoking and nicotine
2010, European Journal of PharmacologyIsoprostanes in fetal and neonatal health and disease
2010, Free Radical Biology and MedicineEffects of early cigarette smoke exposure on early immune development and respiratory disease
2008, Paediatric Respiratory ReviewsCitation Excerpt :Thus, the effects of modifying oxidative function provide a plausible pathway for smoking in modifying the developing immune responses. This is consistent with significantly higher markers of oxidative stress (F2-isoprostane) levels in cord blood from neonates born to smoking mothers (n = 13) compared with non-smoking mothers (n = 28).52 We recently noted that these infants have continued high levels of oxidative stress after birth.53
Nutrition in pediatric lung disease
2007, Paediatric Respiratory ReviewsCitation Excerpt :Furthermore, cord blood catalase, glutathione peroxidase, and glutathione reductase activities were reduced. Other work has found that cord blood F2-isoprostane levels are increased in newborns of smoking mothers.29 Urinary F2-isoprostanes are elevated in 3-month-old infants of smoking mothers, and this correlates with tobacco exposure, as assessed by urinary cotinine levels.23
- 1
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.