Uterine vascular function in a transgenic preeclampsia rat model.

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.