Epithelial Sodium Channel (ENaC) in Endothelium Modulates Vascular Reactivity with a High Salt Diet

Abstract

Recent work has shown that ENaC in the endothelium is involved in vascular dysfunction in the setting of high fat diet and increased aldosterone. However, the effects of endothelial ENaC in the setting of high salt diet (HSD) are unclear, especially in mouse models. Therefore, we aimed to investigate the effects of chronic HSD (8 weeks) on vascular health. Using pressure myography, we found that 8 weeks of HSD significantly reduced acetylcholine (Ach) responsiveness in the thoracodorsal artery (TDA) of mice. This dysfunction was ameliorated when 5mM amiloride, an ENaC inhibitor, was added to the lumen of the vessels. In vessels taken from animals fed a control diet (0.4% NaCl), the addition of amiloride had no effect on Ach‐mediated vasodilation. Additionally, amiloride did not significantly alter sodium nitroprusside or phenylephrine response in the 8 week HSD vessels, suggesting amiloride is directly affecting endothelial function, potentially through altered nitric oxide release. Mice fed an 8 week regimen of HSD had significantly higher serum [Na+] and decreased plasma aldosterone level, suggesting that increased aldosterone is not solely responsible for endothelial ENaC expression. Additionally, an endothelial‐specific deletion of gamma ENaC, generated using an inducible cre‐lox system, appears to offer protection from HSD‐induced vascular dysfunction, as three of six control animals showed decreased responsiveness to Ach with 8 weeks of HSD whereas zero of five knockout animals tested showed endothelial dysfunction. Taken together, these data demonstrate that endothelial ENaC has a role in promoting the vascular dysfunction seen with chronic high salt intake. Ongoing studies are examining the role of ENaC in modulating nitric oxide and eNOS phosphorylation status in the endothelial response to a HSD.Support or Funding InformationNIH P30 2P30DK079307‐11, NIH T32 2T32DK061296‐16This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.