title: Nitric Oxide is a Central Common Metabolite in Vascular Dysfunction Associated with Diseases of Human Pregnancy.
abstract: Preeclampsia (PE), gestational diabetes mellitus (GDM), and maternal supraphysiological hypercholesterolaemia (MSPH) are pregnancy-related conditions that cause metabolic disruptions leading to alterations of the mother, fetus and neonate health. These syndromes result in fetoplacental vascular dysfunction, where nitric oxide (NO) plays a crucial role. PE characterizes by abnormal increase in the placental blood pressure and a negative correlation between NO level and fetal weight, suggesting that increased NO level and oxidative stress could be involved. GDM courses with macrosomia along with altered function of the fetal cardiovascular system and fetoplacental vasculature. Even when NO synthesis in the fetoplacental vasculature is increased, NO bioavailability is reduced due to the higher oxidative stress seen in this disease. In MSPH, there is an early development of atherosclerotic lesions in fetal and newborn arteries, altered function of the fetoplacental vasculature, and higher markers of oxidative stress in fetal blood and placenta, thus, vascular alterations related with NO metabolism occur as a consequence of this syndrome. Potential mechanisms of altered NO synthesis and bioavailability result from transcriptional and post-translational NO synthases (NOS) modulation, including phosphorylation/dephosphorylation cycles, coupling/uncoupling of NOS, tetrahydrobiopterin bioavailability, calcium/calmodulin-NOS and caveolin-1-NOS interaction. Additionally, oxidative stress also plays a role in the reduced NO bioavailability. This review summarizes the available information regarding lower NO bioavailability in these pregnancy pathologies. A common NO-dependent mechanism in PE, GDM and MSPH contributing to fetoplacental endothelial dysfunction is described.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago 8330024, Chile. aaleiva@uc.cl.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.forename: Bárbara
authors.initials: B
authors.lastname: Fuenzalida
authors.forename: Eric
authors.initials: E
authors.lastname: Barros
authors.forename: Bastián
authors.initials: B
authors.lastname: Sobrevia
authors.forename: Rocío
authors.initials: R
authors.lastname: Salsoso
authors.forename: Tamara
authors.initials: T
authors.lastname: Sáez
authors.forename: Roberto
authors.initials: R
authors.lastname: Villalobos
authors.forename: Luis
authors.initials: L
authors.lastname: Silva
authors.forename: Indira
authors.initials: I
authors.lastname: Chiarello
authors.forename: Fernando
authors.initials: F
authors.lastname: Toledo
authors.forename: Jaime
authors.initials: J
authors.lastname: Gutiérrez
authors.forename: Carlos
authors.initials: C
authors.lastname: Sanhueza
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide