RESUMO
Isoflavones are a group of natural phytoestrogens including the compound genistein. Health beneficial effects have been attributed to the consumption of this compound, but the fact that it has estrogen-like activity has raised doubts regarding its potential risk in infants, newborns, or in the fetus and placenta during pregnancy. This work is aimed at studying genistein effects on Ca2+ handling by smooth muscle cells of the human umbilical artery (HUA). Using fluorometric techniques, we found that in these cells genistein reduces the intracellular Ca2+ peak produced by serotonin. The same result could be demonstrated in absence of extracellular Ca2+, suggesting that the isoflavone reduces Ca2+ release from the sarcoplasmic reticulum. Force measurement experiments strengthen these results, since genistein reduced the peak force attained by intact HUA rings stimulated by serotonin in a Ca2+-free solution. Moreover, genistein induced the relaxation of HUA rings precontracted either with serotonin or a depolarizing high-extracellular K+ solution, hinting at a reduction of extracellular Ca2+ entry to the cell. This was confirmed by whole-cell patch-clamp experiments where it was shown that the isoflavone inhibits ionic currents through voltage-operated Ca2+ channels. In summary, we show that genistein inhibits two mechanisms that could increase intracellular Ca2+ in human umbilical smooth muscle cells, behaving in this way as a potential vasorelaxing substance of fetal vessels. Taking into account that genistein is able to cross the placental barrier, these data show that isoflavones may have important implications in the regulation of feto-maternal blood flow in pregnant women who consume soy-derived products as part of their meals.
Assuntos
Cálcio/metabolismo , Genisteína/farmacologia , Canais de Cálcio/efeitos dos fármacos , Feminino , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Técnicas de Patch-Clamp , Gravidez , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Artérias Umbilicais/metabolismoRESUMO
The objective of this study was to evaluate the effect of maternal smoking during pregnancy on the risk of intracranial hemorrhage in preterm infants (born at 24 to 33 weeks of gestation). We conducted a case-control study of 96 preterm infants with intracranial hemorrhage and 96 gestational age-matched control subjects with negative cranial ultrasonographic findings. In conditional multiple logistic regression models, heavy maternal smoking ( > 10 cigarettes per day) during the latter half of pregnancy was associated with an increased risk of mild (grade I or II) intracranial hemorrhage (odds ratio = 5.96, 95% confidence interval 1.72 to 20.76; p = 0.005). After adjustment for the confounding effect of birth weight and respiratory distress syndrome, the risk of any intracranial hemorrhage (grade I to IV) was three times higher (adjusted odds ratio = 3.63, 95% confidence interval 1.37 to 9.63; p = 0.009) in infants of heavy smokers ( > 10 cigarettes per day) than in control subjects. The results of this study indicate that cigarette smoking during the latter half of pregnancy increases the risk of intracranial hemorrhage in preterm infants. The deleterious effect of smoking was greater for mild hemorrhages (grade I or II) and was confined to infants of heavy smokers.