title: Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero.
abstract: 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.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Hooper
authors.affiliation: Department of Pediatrics, University of Colorado, Denver, Colorado;
authors.forename: Cassidy
authors.initials: C
authors.lastname: Delaney
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Taylor
authors.initials: T
authors.lastname: Streeter
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Yarboro
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Stanley
authors.initials: S
authors.lastname: Poole
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Naoko
authors.initials: N
authors.lastname: Brown
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee;
authors.forename: Robert B
authors.initials: RB
authors.lastname: Cotton
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jeff
authors.initials: J
authors.lastname: Reese
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; Elaine.L.Shelton@vanderbilt.edu.
authors.forename: Elaine L
authors.initials: EL
authors.lastname: Shelton
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D009213:Myography; D010547:Persistent Fetal Circulation Syndrome; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D005473:Fluoxetine; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
keywords: PPHN; SSRI; ductus arteriosus; fluoxetine; mouse; serotonin; sertraline