AUTHOR=Sternak Magdalena , Bar Anna , Adamski Mateusz G. , Mohaissen Tasnim , Marczyk Brygida , Kieronska Anna , Stojak Marta , Kus Kamil , Tarjus Antoine , Jaisser Frederic , Chlopicki Stefan 

TITLE=The Deletion of Endothelial Sodium Channel α (αENaC) Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00178

DOI=10.3389/fphar.2018.00178

ISSN=1663-9812

ABSTRACT=The role of Epithelial sodium channel (ENaC) activity in the regulation of endothelial function is not clear. 
Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaC KO mice) using unique MRI-based analysis of acetylcholine- and flow-mediated dilation as well as vascular permeability. Mice were challenged or not with Lipopolysaccharide (LPS, from Salmonella enterica serotype abortus equi, 10 mg/kg, i.p.). In addition, changes in vascular permeability were analyzed by Evans Blue assay in ex vivo organs, while changes in vascular permeability were determined by a FITC-dextran-based assay in perfused mesenteric artery. 
In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaC KO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaC KO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxaemic endo-αENaC KO vs. control mice. The impaired endothelial function in endotoxaemia in endo-αENaC KO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. 
In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxaemia.