title: The significance of endothelin in platelet-activating factor-induced fetal growth restriction.
abstract: The significance of endothelin-1 (ET-1) in platelet-activating factor (PAF)-induced fetal growth restriction (FGR) was evaluated in timed-pregnant rats receiving intravenous carbamyl-PAF (c-PAF; 0.5, 1.0, or 2.5 µg/kg per h) or vehicle, with or without ET-1 receptor A (ET(A)) antagonist (10 or 20 mg/kg per d) for 7 days beginning on gestation day 14. Tissues were collected on day 21. Carbamyl-PAF reduced fetal weights dose dependently. Placental weights were significantly reduced but not dose dependently. ET(A) antagonism prevented FGR at the 0.5, but not the 1.0 and 2.5 µg/kg per h c-PAF doses. Correspondingly, placental, but not uterine, preproET-1 messenger RNA (mRNA) expression (determined by reverse transcription-polymerase chain reaction) was increased at 0.5 µg/kg per h but not at higher c-PAF doses. In summary, c-PAF infusion results in fetal and placental growth restriction in the rat. At low doses of c-PAF, ET-1 is central to the pathophysiology of PAF-induced FGR. At higher c-PAF doses, FGR is induced by mechanisms other than ET-1 action.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, NorthShore University HealthSystem, Evanston, IL 60201, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Neerhof
authors.forename: Saira
authors.initials: S
authors.lastname: Khan
authors.forename: Sylvia
authors.initials: S
authors.lastname: Synowiec
authors.forename: Xiao-Wu
authors.initials: XW
authors.lastname: Qu
authors.forename: Larry G
authors.initials: LG
authors.lastname: Thaete
mesh_terms: D000818:Animals; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D020567:Fetal Weight / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000033:anatomy & histology / Q000737:chemistry; D010972:Platelet Activating Factor / Q000008:administration & dosage*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010972:Platelet Activating Factor; D012333:RNA, Messenger