Acute exposure to iron (II) impairs the vascular endothelial structure and function.

Although chronic iron overload is associated with vasculopathy, the direct effect of excessive iron on the vasculature during acute poisonings remains unknown. Thus, we tested whether ex vivo exposure of rat arteries to high concentrations of ferrous iron (Fe) impairs endothelial structure and function, and explored the involvement of reactive oxygen species (ROS) in these effects. Aortic segments from rats were used to assess vascular reactivity, ROS production and endothelial structure after 30-min incubation with FeSO. Fe exposure increased the contractile vasoreactivity in a concentration-dependent manner and impaired endothelium-dependent vasodilation at higher concentrations (100 and 1000 µM). The attenuated effects of endothelial removal and L-NAME incubation on the vasoreactivity of Fe-exposed aortas suggested a reduced endothelial modulation of vascular tone, accompanied by decreased nitric oxide (NO) bioavailability, as detected by a fluorescent probe. Furthermore, the production of hydroxyl radical (OH·) and hydrogen peroxide (HO) was increased by Fe, while superoxide anion (O) levels remained unchanged. Supporting the involvement of OH· and HO, Fe-induced hyperreactivity was partially reversed by co-incubation with DMSO and catalase, respectively. Microstructural analysis revealed iron deposits on the endothelial surface after incubation with Fe 100 µM, and endothelial cell denudation in aortic segments acutely exposed to Fe 1000 µM. In conclusion, acute ex vivo Fe exposure causes concentration-dependent damage to endothelial cells, resulting in impaired endothelial modulation of the vascular tone. The mechanism involves decreased NO bioavailability associated with increased ROS production, indicating a direct detrimental effect of excess iron to the vasculature.