Published Online
on January 14, 2008

A more recent version of this article appeared on February 1, 2008

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Submitted on October 12, 2007
Revised on November 6, 2007

Uterine Vascular Function in a Transgenic Preeclampsia Rat Model

Stefan Verlohren; Manuela Niehoff; Lydia Hering; Nele Geusens; Florian Herse; Andrei N. Tintu; Andreas Plagemann; Ferdinand LeNoble; Robert Pijnenborg; Dominik N. Muller; Friedrich C. Luft; Joachim W. Dudenhausen; Maik Gollasch; and Ralf Dechend^*

From the Departments of Obstetrics (S.V., M.N., A.P., J.W.D.), and Nephrology (M.G.), and Department of Cardiology, Franz Volhard Clinic, HELIOS Klinikum Berlin-Buch (F.H., R.D.), Charité University Medicine, Berlin, Germany; Experimental and Clinical Research Center (F.C.L.), Max Delbrueck Center for Molecular Medicine (S.V., L.H., A.N.T., F.L., D.N.M., F.C.L.), Berlin, Germany; and the Department of Gynecology and Obstetrics (N.G., R.P.), University of Leuven, Leuven, Belgium.

^* To whom correspondence should be addressed. E-mail: ralf.dechend{at}charite.de.

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 F1):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.

Key words: preeclampsia • uterine artery • rat • endothelial dysfunction • intrauterine growth restriction • Doppler ultrasound

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