Department of Physiological Sciences, Biological Sciences Center, State University of Londrina, Parana, Brazil.
Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Parana, Brazil.
Eur J Pharmacol. 2017 Oct 15;813:147-152. doi: 10.1016/j.ejphar.2017.08.018. Epub 2017 Aug 17.
Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation. The experiments were performed in adult male offspring, treated or not with reserpine (4mg/Kg, ip, 28h before the experimental protocol). Fluoxetine and control rats were submitted to a single restraint stress session (ST) for 1h. Curves to phenylephrine were performed in thoracic aorta with endothelium. Aortic nitric oxide (NOx) were evaluated by the Griess method. The aortic contraction induced by phenylephrine was similar between control and fluoxetine rats. The acute stress reduced contraction in aorta of control ST compared to control, and L-NAME equaled this response. In fluoxetine rats, ST did not change the aortic constriction. Reserpine treatment restored the vasoconstriction in control ST, but did not interfere with aortic contraction in control, fluoxetine or fluoxetine ST. The NOx concentration was higher in aortas from control ST than control rats, and reserpine reduced NOx levels of control ST. The NOx concentration was similar between fluoxetine and fluoxetine ST rats, treated or not with reserpine. In conclusion, maternal treatment with fluoxetine blunted acute restraint stress-induced NO system activation and aortic adaptation in adult offspring.
选择性 5-羟色胺再摄取抑制剂是妊娠期女性最常开的抗抑郁药。母亲用氟西汀治疗会使胎儿和新生儿暴露在更高水平的 5-羟色胺中，5-羟色胺在应激反应中起作用。因此，本研究旨在评估母体用氟西汀治疗是否会干扰急性束缚应激后成年雄性子代的主动脉反应性。Wistar 大鼠在妊娠期和哺乳期用氟西汀（5mg/kg/天）或水（对照）灌胃。在成年雄性子代中进行实验，用或不用利血平（4mg/kg，ip，实验方案前 28h）预处理。氟西汀和对照大鼠接受单次束缚应激 1h。用内皮完整的胸主动脉进行苯肾上腺素曲线。用 Griess 法评估主动脉一氧化氮（NOx）。苯肾上腺素诱导的主动脉收缩在对照和氟西汀大鼠之间相似。急性应激使对照 ST 的主动脉收缩减少，与对照相比，L-NAME 相等。在氟西汀大鼠中，ST 未改变主动脉收缩。利血平处理恢复了对照 ST 的血管收缩，但未干扰对照、氟西汀或氟西汀 ST 的主动脉收缩。对照 ST 的主动脉中 NOx 浓度高于对照大鼠，利血平降低了对照 ST 的 NOx 水平。氟西汀和氟西汀 ST 大鼠的 NOx 浓度相似，无论是否用利血平处理。结论：母体用氟西汀治疗使成年子代急性束缚应激诱导的 NO 系统激活和主动脉适应性减弱。
