Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero.

Hooper CW, Delaney C, Streeter T, Yarboro MT, Poole S, Brown N, Slaughter JC, Cotton RB, Reese J, Shelton EL
Am J Physiol Heart Circ Physiol. 2016 311 (3): H572-81

PMID: 27371685 · PMCID: PMC5142184 · DOI:10.1152/ajpheart.00822.2015

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.

Copyright © 2016 the American Physiological Society.

MeSH Terms (17)

Animals Aorta Ductus Arteriosus Female Fluoxetine Immunohistochemistry Mice Myography Persistent Fetal Circulation Syndrome Pregnancy Real-Time Polymerase Chain Reaction Receptors, Serotonin Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Serotonin Uptake Inhibitors Sertraline Vasoconstriction

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