Role of Reactive Oxygen Species During Hypertension in Response to Chronic Antiangiogenic Factor (sFlt-1) Excess in Pregnant Rats

BACKGROUND Preeclampsia is associated with increased levels of reactive oxygen species (ROS) and the antiangiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1). Moreover, recent studies have indicated that chronic sFlt-1 excess causes hypertension in pregnant animals. The purpose of this study was to evaluate the role of ROS in mediating sFlt-1-induced hypertension in the pregnant rat. METHODS Mean arterial pressure (MAP), and plasma sFlt-1 and tissue ROS levels were measured in the following groups: (i) pregnant controls; (ii) sFlt-1-treated pregnant rats; (iii) Tempol-treated pregnant rats; (iv) sFlt-1- and Tempol-treated pregnant rats. RESULTS MAP increased from 104 +/- 2 mm Hg in pregnant control rats to 118 +/- 3 mm Hg (P = 0.002) in sFlt-1-infused rats. Basal and nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated levels of tissue ROS were increased in response to excess sFlt-1 during pregnancy. Pretreatment with Tempol attenuated oxidative stress and hypertension in response to sFlt-1. CONCLUSIONS ROS play an important role in mediating hypertension in response to chronic sFlt-1 excess during pregnancy.