Evaluation of the effects of nitric oxide derived from sodium nitrite on angiogenic and antiangiogenic factors in gestational hypertension induced by placental ischemia in rats

Abstract

The gestational period is marked by several systemic adaptations, including cardiovascular, necessary for the development of a healthy pregnancy, meeting the fetal metabolic demand.Preeclampsia (PE) is a condition that occurs during pregnancy in which trophoblastic invasion and the formation of blood vessels at the maternal-fetal interface are impaired by factors that are still unclear. These changes act by decreasing the passage of placental blood flow, causing hypoxia and ischemia, resulting in an increase in maternal blood pressure, which may worsen fetal development. The changes caused by preeclampsia can be modulated by endogenous or exogenous nitric oxide (NO) - which acts as a potent vasodilator -, being an interesting alternative for changes in blood pressure. The experimental model of induction of gestational hypertension known as RUPP (Reduced Uteroplacental Perfusion Pressure) has been indicated as one of the best methods for demonstrating most of the responses observed in human preeclampsia. Assuming that the RUPP model decreases the concentration of nitric oxide and that the administration of sodiumnitrite through the oral route is capable of causing changes in blood pressure, the objective of this study is to analyze whether the ingestion of sodium nitrite, after the induction of arterialhypertension, is able to balance the angiogenic and antiangiogenic factors, promoting the reconstitution of the maternal-fetal interface. For this, 40 Wister rats will be divided into fourdifferent groups: normotensive pregnant rats (group 1), normotensive pregnant rats treated withsodium nitrite (group 2), hypertensive pregnant rats (group 3) and hypertensive pregnant ratstreated with sodium nitrite (group 4). Arterial hypertension will be induced by the RUPP surgicalmodel. On the 20th day of gestation, the rats will be anesthetized and euthanized, and samples ofuterus, placenta, thoracic artery and abdominal artery will be collected for the analysis ofbiochemical and molecular parameters, investigating the concentrations of angiogenic and nonangiogenic factors such as PLGF (Placental Growth Factor), VEGF (Vascular Endothelial GrowthFactor), sFlt-1 (Soluble Tyrosine Kinase-1) and sEng (Soluble Endoglin).