Nitric oxide (NO) bioavailability is fundamental in the regulation of redox balance
and functionality of the endothelium, especially in the case of the umbilical cord
(UC), which has no innervation. The analysis of UC vessel-related complications could
serve as a useful tool in the understanding of the pathophysiological mechanisms leading
to neonatal cardiovascular disorders. Therefore, the aim of this study was to characterize
the mechanisms that rule the severity of prenatal endothelial dysfunction, induced
by the long-term effect of maternal smoking. Our analysis describes the initiation
and the consequences of endothelial nitric oxide synthase (NOS3) deactivation, along
with the up-regulation of possible compensatory pathways, using structural, molecular
and biochemical approaches. This study was carried out on both the UC arteries and
veins originated from neonates born to non-smoking and heavy-smoking mothers. The
alterations stimulated by maternal smoking are vessel-specific and proportional to
the level of exposure to harmful materials passed through the placenta. Typically,
in the primarily exposed veins, an increased formation of reactive oxygen species
and an up-regulation of the highly-efficient NOS2-NO producing pathway were detected.
Despite all the extensive structural and functional damages, the ex vivo heat and
cadmium ion-treated UC vein pieces still support the potential for stress response.
