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.