title: Sensitivity to the thromboxane A2 analog U46619 varies with inner diameter in human stem villous arteries.
abstract: BACKGROUND
  The vascular resistance of stem villous arteries is determined by the balance between different contractile and relaxant agents and in the utero-placental circulation. Thromboxane A2 (TxA2), prostaglandin F2α (PGF2α) and endothelin-1 (ET-1) are considered to be among the most important contractile factors. However, it is not known if their contractile effects are consistent along the villous tree. We hypothesized that the sensitivity to different agonists could be influenced by artery diameter and thus that their contribution to placental vascular resistance may differ.
  
  
  METHODS
  Using an isometric wire myograph, the contractility and sensitivity (pD2) to the thromboxane A2 mimetic U46619, PGF2α and ET-1 were investigated in isolated human stem villous arteries and human uterine fundus and isthmus arteries obtained from healthy, pregnant women who had experienced uncomplicated pregnancy.
  
  
  RESULTS
  In fetal arteries, the pD2 values for U46619 correlated positively with arterial diameter with no such dependence observed for ET-1 and PGF2α. In maternal arteries, pD2 remained constant for all the agonists tested despite highly variable vessel diameter.
  
  
  CONCLUSIONS
  A selective decrease in sensitivity to TxA2 receptor stimulation was observed with decreasing vascular diameter in human stem villous arteries. The contractile factors PGF2α and ET-1 show no such relationship.
authors.affiliation: Aarhus University Hospital, Department of Clinical Medicine - Obstetrics and Gynaecology, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark; Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1170, 8000 Aarhus C, Denmark. Electronic address: thbr@clin.au.dk.
authors.forename: Torbjoern
authors.initials: T
authors.lastname: Broegger
authors.affiliation: Aarhus University Hospital, Department of Clinical Medicine - Obstetrics and Gynaecology, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark; Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1170, 8000 Aarhus C, Denmark; Aarhus University, Aarhus Institute of Advanced Studies, Hoegh-Guldbergs Gade 6B 8000 Aarhus C, Denmark. Electronic address: kea@aias.au.dk.
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.affiliation: Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1170, 8000 Aarhus C, Denmark. Electronic address: ca@biomed.au.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Aalkjaer
authors.affiliation: Aarhus University Hospital, Department of Clinical Medicine - Obstetrics and Gynaecology, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark. Electronic address: af@clin.au.dk.
authors.forename: Axel
authors.initials: A
authors.lastname: Forman
authors.affiliation: Aarhus University Hospital, Department of Clinical Medicine - Obstetrics and Gynaecology, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark; Aarhus University, Department of Biomedicine, Ole Worms Allé 3, Building 1170, 8000 Aarhus C, Denmark. Electronic address: db@biomed.au.dk.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Boedtkjer
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D001158:Arteries / Q000033:anatomy & histology* / Q000187:drug effects*; D002824:Chorionic Villi / Q000098:blood supply* / Q000187:drug effects; D015237:Dinoprost / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006801:Humans; D011247:Pregnancy; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists*; D013928:Thromboxane A2 / Q000031:analogs & derivatives*; D014599:Uterus / Q000098:blood supply / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D019332:Endothelin-1; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost
keywords: Human placenta; Pharmacology; Placental perfusion; Stem villous arteries; Thromboxane A(2)