Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia

Abstract

Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2−) rapidly inactivates NO and forms peroxynitrite (ONOO−). It is known that ONOO− accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE.

An increased population of regulatory T cells improves the pathophysiology of placental ischemia in a rat model of preeclampsia

“…Placental oxidative stress has been shown to be increased in preeclamptic women, and placental and renal oxidative stress is observed in preclinical models preeclampsia, and it is implicated in contributing to the development of vascular dysfunction, proteinuria, and hypertension during pregnancy (9,13,27,28). Importantly reactive oxygen species (ROS) is a byproduct of inflammation and is elevated in response to RUPP CD4ϩ T cells and IL-17-and AT 1 -AA-induced hypertension during pregnancy.…”

Altered Retinal Flicker Response Indicates Microvascular Dysfunction in Women With Preeclampsia

“…1 It is considered as a disease of the maternal endothelium, 2 and the proper function of any endothelium includes maintenance of a barrier and regulation of vascular tone. In preeclampsia, vasoactive substances, such as sFlt-1, are released into the maternal circulation, 3 resulting in reduced nitric oxide (NO) bioavailability, 4 vasoconstriction of the microvasculature, increased peripheral resistance, and hypertension. 5 Several attempts have been described to quantify the degree of peripheral vascular resistance, endothelial dysfunction (EDF), and microvascular constriction indirectly; however, a direct method of visualizing and measuring microvascular changes during pregnancy may advance understanding of the development of preeclampsia and support clinical risk stratification in pregnancy.…”

Inducible nitric oxide synthase in the placenta of pregnant women with preeclampsia

“…However, there is controversy about the same levels in relation to the PEC, because some studies report increased expression of iNOS, still others have found the opposite [11,12,13].…”

“…Finding increased expression of iNOS and eNOS in placenta of women with PEC [11]. Perhaps related to alterations in the bioavailability of nitric oxide, being the inflammatory process induces iNOS [12].…”