title: Uterine vascular function in a transgenic preeclampsia rat model.
abstract: We investigated intrauterine growth restriction, endothelial function, and uterine artery blood flow characteristics in a transgenic preeclampsia rat model with an activated renin-angiotensin system. We compared preeclamptic Sprague-Dawley (SD-PE) rats with normal pregnant Sprague-Dawley and nonpregnant Sprague-Dawley rats. We used transabdominal ultrasound and found that SD-PE rat embryos developed intrauterine growth restriction. Isolated uterine arteries from SD-PE rats incubated with phenylephrine exhibited an increased contractile response, whereas a single high dose of acetylcholine resulted in an impaired vasorelaxation compared with controls. Incremental acetylcholine doses increased relaxation of SD-PE vessels at low acetylcholine doses but caused a paradoxical contraction at higher acetylcholine doses. Indomethacin and a thromboxane-receptor antagonist (SQ 29,548) blocked this effect, suggesting maternal prostanoid-dependent endothelial dysfunction. SD-PE rats had a decreased prostacyclin (6-keto-prostaglandin F1alpha):thromboxane ratio in the serum compared with normal pregnant Sprague-Dawley rats or nonpregnant Sprague-Dawley. Surprisingly, the Doppler resistance index decreased during pregnancy in SD-PE compared with normal pregnant Sprague-Dawley rats, suggesting unimpaired uteroplacental flow in the uterine artery. Umbilical flow was unchanged with absent end-diastolic flow in all of the groups. Renin-angiotensin system activation-induced preeclampsia is associated with altered placentation, modified resistance index, and endothelial dysfunction. A disturbed prostacyclin:thromboxane ratio could be an important mediator.
authors.affiliation: Department of Obstetrics, Franz Volhard Clinic, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Verlohren
authors.forename: Manuela
authors.initials: M
authors.lastname: Niehoff
authors.forename: Lydia
authors.initials: L
authors.lastname: Hering
authors.forename: Nele
authors.initials: N
authors.lastname: Geusens
authors.forename: Florian
authors.initials: F
authors.lastname: Herse
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Tintu
authors.forename: Andreas
authors.initials: A
authors.lastname: Plagemann
authors.forename: Ferdinand
authors.initials: F
authors.lastname: LeNoble
authors.forename: Robert
authors.initials: R
authors.lastname: Pijnenborg
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Dudenhausen
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001808:Blood Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D011464:Epoprostenol / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000000981:diagnostic imaging / Q000209:etiology; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012084:Renin-Angiotensin System; D013931:Thromboxanes / Q000097:blood; D016216:Ultrasonography, Prenatal; D014599:Uterus / Q000098:blood supply*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D011464:Epoprostenol; D000109:Acetylcholine