Hooper Christopher W, Delaney Cassidy, Streeter Taylor, Yarboro Michael T, Poole Stanley, Brown Naoko, Slaughter James C, Cotton Robert B, Reese Jeff, Shelton Elaine L
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
Department of Pediatrics, University of Colorado, Denver, Colorado;
Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H572-81. doi: 10.1152/ajpheart.00822.2015. Epub 2016 Jul 1.
Use of selective serotonin reuptake inhibitors (SSRIs) is common during pregnancy. Fetal exposure to SSRIs is associated with persistent pulmonary hypertension of the newborn (PPHN); however, a direct link between the two has yet to be established. Conversely, it is well known that PPHN can be caused by premature constriction of the ductus arteriosus (DA), a fetal vessel connecting the pulmonary and systemic circulations. We hypothesized that SSRIs could induce in utero DA constriction. Using isolated vessels and whole-animal models, we sought to determine the effects of two commonly prescribed SSRIs, fluoxetine and sertraline, on the fetal mouse DA. Cannulated vessel myography studies demonstrated that SSRIs caused concentration-dependent DA constriction and made vessels less sensitive to prostaglandin-induced dilation. Moreover, in vivo studies showed that SSRI-exposed mice had inappropriate DA constriction in utero. Taken together, these findings establish that SSRIs promote fetal DA constriction and provide a potential mechanism by which SSRIs could contribute to PPHN.
孕期使用选择性5-羟色胺再摄取抑制剂（SSRI）很常见。胎儿接触SSRI与新生儿持续性肺动脉高压（PPHN）有关；然而，两者之间的直接联系尚未确立。相反，众所周知，PPHN可由动脉导管（DA）过早收缩引起，DA是连接肺循环和体循环的胎儿血管。我们推测SSRI可诱导子宫内DA收缩。利用离体血管和整体动物模型，我们试图确定两种常用的SSRI，即氟西汀和舍曲林，对胎鼠DA的影响。插管血管肌动描记术研究表明，SSRI引起浓度依赖性DA收缩，并使血管对前列腺素诱导的扩张不那么敏感。此外，体内研究表明，接触SSRI的小鼠在子宫内DA收缩不当。综上所述，这些发现证实SSRI可促进胎儿DA收缩，并提供了一种潜在机制，通过该机制SSRI可能导致PPHN。
