title: Pregnancy Augments G Protein Estrogen Receptor (GPER) Induced Vasodilation in Rat Uterine Arteries via the Nitric Oxide - cGMP Signaling Pathway.
abstract: BACKGROUND
  The regulation of vascular tone in the uterine circulation is a key determinant of appropriate uteroplacental blood perfusion and successful pregnancy outcome. Estrogens, which increase in the maternal circulation throughout pregnancy, can exert acute vasodilatory actions. Recently a third estrogen receptor named GPER (G protein-coupled estrogen receptor) was identified and, although several studies have shown vasodilatory effects in several vascular beds, nothing is known about its role in the uterine vasculature.
  
  
  OBJECTIVE
  The aim of this study was to determine the function of GPER in uterine arteries mainly during pregnancy. Uterine arteries were isolated from nonpregnant and pregnant rats.
  
  
  METHODS
  Vessels were contracted with phenylephrine and then incubated with incremental doses (10-12-10-5 M) of the selective GPER agonist G1.
  
  
  RESULTS
  G1 induced a dose-dependent vasodilation which was: 1) significantly increased in pregnancy, 2) endothelium-dependent, 3) primarily mediated by NO/cGMP pathway and 4) unaffected by BKca channel inhibition.
  
  
  CONCLUSIONS
  This is the first study to show the potential importance of GPER signaling in reducing uterine vascular tone during pregnancy. GPER may therefore play a previously unrecognized role in the regulation of uteroplacental blood flow and normal fetus growth.
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tropea
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Ernestina Marianna
authors.initials: EM
authors.lastname: De Francesco
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rigiracciolo
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.affiliation: Maternal and Fetal Health Research Centre, The University of Manchester, Manchester, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Wareing
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Osol
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mandalà
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D009569:Nitric Oxide / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D055988:Uterine Artery / Q000166:cytology / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
chemical_list: C520305:Gper1 protein, rat; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D006152:Cyclic GMP