Uterine vascular function in a transgenic preeclampsia rat model

Hypertension. 2008 Feb;51(2):547-53. doi: 10.1161/HYPERTENSIONAHA.107.103176. Epub 2008 Jan 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acetylcholine / pharmacology
  • Animals
  • Animals, Genetically Modified
  • Arteries / drug effects
  • Arteries / physiopathology
  • Blood Vessels / diagnostic imaging
  • Blood Vessels / physiopathology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiopathology
  • Epoprostenol / blood
  • Female
  • Fetal Growth Retardation / diagnostic imaging
  • Fetal Growth Retardation / etiology
  • In Vitro Techniques
  • Male
  • Phenylephrine / pharmacology
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow
  • Renin-Angiotensin System
  • Thromboxanes / blood
  • Ultrasonography, Prenatal
  • Uterus / blood supply*
  • Vascular Resistance
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Thromboxanes
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Phenylephrine
  • Epoprostenol
  • Acetylcholine