1. Selective serotonin reuptake inhibitor exposure constricts the mouse ductus arteriosus in utero
- Author
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Robert B. Cotton, Stanley D. Poole, Taylor Streeter, Cassidy Delaney, Elaine L. Shelton, Naoko Brown, Christopher W. Hooper, Jeff Reese, James C. Slaughter, and Michael T. Yarboro
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Physiology ,Serotonin reuptake inhibitor ,030204 cardiovascular system & hematology ,Pharmacology ,Real-Time Polymerase Chain Reaction ,Persistent Fetal Circulation Syndrome ,behavioral disciplines and activities ,Constriction ,Mice ,03 medical and health sciences ,Integrative Cardiovascular Physiology and Pathophysiology ,0302 clinical medicine ,Pregnancy ,Fluoxetine ,Sertraline ,Physiology (medical) ,Internal medicine ,Ductus arteriosus ,mental disorders ,medicine ,Animals ,cardiovascular diseases ,RNA, Messenger ,Aorta ,Fetus ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,digestive, oral, and skin physiology ,Myography ,Ductus Arteriosus ,Immunohistochemistry ,medicine.anatomical_structure ,Endocrinology ,Vasoconstriction ,Receptors, Serotonin ,embryonic structures ,cardiovascular system ,Female ,Serotonin ,Cardiology and Cardiovascular Medicine ,business ,Selective Serotonin Reuptake Inhibitors ,030217 neurology & neurosurgery ,medicine.drug - 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.
- Published
- 2016