Prostaglandin E₂ in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E₂ Formation by Nicotine and Cotinine

Abstract

Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E₂ (PGE₂) which induces labor, initiates uterine contractions and maintains the homeostasis of placental blood flow. Therefore, we studied: (a) the influence of nicotine and cotinine on the effects of PGE₂ on placental vasculature in perfused human placental cotyledon, and (b) the activation of placental phospholipase A₂ (PLA₂) by nicotine and cotinine using 1-palmitoyl-2-[1-¹⁴C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These studies revealed that: (1) increasing concentrations of PGE₂ (10– 150 ng/ml) increased umbilical perfusion pressure by 170 ± 10% (n = 6) of control (100%). Cotinine (2 µg/ml) enhanced this effect at all concentrations of PGE₂. Nicotine (2 µg/ml) prevented the effect of PGE₂; (2) both cotinine (EC₅₀ 470–500 fmol/l) and nicotine (EC₅₀ 18–32 pmol/l) activated PLA₂ in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA₂ and potentiating the vasoconstrictive effects of PGE₂ on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator of placental arteries. Acetylcholine stimulates muscarinic receptors of endothelial cells resulting in the release of endothelium-derived relaxing factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or abolishes the vasoconstrictive effects of PGE₂ through the release of EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE₂ and induction of preterm labor and spontaneous abortions.

Prostaglandin E2in the expired breath condensate of patients with asthma

“…The results presented here show that smoking significantly increased the levels of PGE 2 in asthmatic subjects, even compared to normal smoking subjects. This might be explained by previous observations that cigarette smoke stimulates the formation of PGs in alveolar macrophages, that long-term 100 120 80 nicotine substitution diminishes the beneficial effects of smoking cessation due to the possible stimulatory effects of nicotine and cotinine on eicosanoid synthesis even in vivo [22], and, finally, that accumulation of cotinine, the major metabolite of nicotine, in foetal circulation contributes to production of PGE 2 [23].…”

Obstetric and perinatal effects of active and/or passive smoking during pregnancy

“…Cotinine, a metabolite of nicotine, enhances the vasoconstrictive action of prostaglandin E2 and the accumulation of cotinine in the fetal bloodstream may contribute towards inducing labor prematurely and spontaneous abortion among smokers. 16 We know that when cigarettes are incompletely burned, there is the production of carbon monoxide, a substance that presents Note: ectopic and pathological pregnancies terminated before delivery and infants whose birth weight we could not determine were excluded. p < 0.01: non-smokers ≠ active + passive smokers and non-smokers ≠ passive smokers.…”

A narrative review of medical, chiropractic, and alternative health practices in the treatment of primary dysmenorrhea

“…Former research hypothesizes that direct cigarette smoking constricts uterine blood vessels and is a contributing factor in cases of spontaneous abortions or low birth weight infants. 18,19 Direct inhalation or second hand inhalation may threaten a person's long-term health aside from the development of respiratory conditions. Inhalation of second hand smoke was found to increase the occurrence of pelvic pain in nonsmoking, newly wed females with no history of dysmenorrhea.…”