Maternal dexamethasone increases endothelin-1 sensitivity and endothelin a receptor expression in ovine foetal placental arteries.
Despite National Institutes of Health recommendations to administer antenatal steroids as a single course to women threatening preterm delivery, repeated treatments are often given. We investigated effects of repeated dexamethasone (DM) administered to the ewe on small maternal and foetal placental arteries. We hypothesized that DM would increase responsiveness to endothelin-1 (ET-1) and norepinephrine (NE) and that foetal arteries would react differently to ET-1 and NE compared to maternal arteries. Ewes received three treatments beginning at 103, 110, and 117 days of gestation (dGA). Each treatment consisted of four IM injections of 2mg DM or saline at 12-h intervals. At 119 dGA, in vitro functional studies were performed using Mulvany wire myography and endothelin receptor (ETR) expression was quantified using real-time RTPCR and receptor ligand autoradiography. Foetal placental arteries demonstrated greater maximal contractility to ET-1 and lesser maximal contractility to NE compared to maternal arteries. DM increased the maximal contraction elicited by ET-1 and NE in foetal but not maternal placental arteries. DM also increased the abundance of type-A ETR but not type-B ETR mRNA in foetal but not maternal placental arteries. However, within the whole placentome, DM increased the abundance of type-B ETR and decreased type-A ETR mRNA, which was confirmed by similar changes in ETR binding specifically within the labyrinth region. In summary, repeated DM treatment results in agonist and vascular bed specific responses within the placenta.
Kutzler
M A
MA
Department of Clinical Sciences, Oregon State University College of Veterinary Medicine, 158 Magruder Hall, Corvallis, OR 97331, USA. michelle.kutzler@oregonstate.edu
Molnar
J
J
Schlafer
D H
DH
Kuc
R E
RE
Davenport
A P
AP
Nathanielsz
P W
PW
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D003656:Decidua / Q000098:blood supply / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D009638:Norepinephrine / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D021041:Placental Circulation / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D014327:Trophoblasts / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D003907:Dexamethasone; D009638:Norepinephrine