Angiogenesis inhibition causes hypertension and placental dysfunction in a rat model of preeclampsia

• Background Preeclampsia is a serious pregnancy complication, accompanied by increased maternal and fetal morbidity. Different models have been used to study preeclampsia, but none of these display all the key features of the disease. Method We investigated the effects on maternal blood pressure and fetal outcome exerted by the angiogenesis inhibitor Suramin (1100 mg/kg i.p.) during early placentation. Blood pressure and heart rate were measured continuously with telemetry in Sprague - Dawley rats of four experimental groups: nonpregnant controls, Suramin-treated nonpregnant rats, pregnant controls and pregnant Suramin-treated rats. Blood samples were collected before pregnancy and at gestational day 20 for analysis of renin and sFIt-1. The fetal and placental morphology were evaluated after caesarian section on gestational day 20. Results The blood pressure of the pregnant Suramin-treated rats successively increased during pregnancy and differed by 17 mmHg at gestational day 20 compared with the pregnant control rats. In the pregnant Suramin-treated rats group, the renin levels increased (+122%) and the sFIt-1 levels decreased (-58%) during pregnancy. The pregnant Suramin-treated fetuses and placentae were smaller (2.8 g and 0.51 g) than the pregnant controls rats' fetuses and placentae (3.5g and 0.56g). Resorptions tended to be higher in the pregnant Suramin-treated rat litters compared with the pregnant control rat litters (P = 0.08). The area of the maternal blood vessels in the mesometrial triangle was smaller in the pregnant Suramin-treated rats group than in the pregnant control rats group. Conclusion The inhibition of uterine angiogenesis increases maternal blood pressure and compromises fetal and placental development. Placental hypoxia and subsequent activation of the renin-angiotensin system may play an important role for the hypertension. J Hypertens 27:829-837 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Nyckelord

blood pressure

fetal growth retardation

pregnancy

renin

soluble fms-like tyrosine kinase 1

suramin

telemetry

vascular endothelial growth factor

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MEDICIN

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