| First Author | Tarjus A | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 13 | PubMed ID | 31252520 |
| Mgi Jnum | J:289271 | Mgi Id | MGI:6434931 |
| Doi | 10.3390/ijms20133132 | Citation | Tarjus A, et al. (2019) The Absence of Endothelial Sodium Channel alpha (alphaENaC) Reduces Renal Ischemia/Reperfusion Injury. Int J Mol Sci 20(13):3132 |
| abstractText | The epithelial sodium channel (ENaC) has a key role in modulating endothelial cell stiffness and this in turn regulates nitric oxide (NO) synthesis. The physiological relevance of endothelial ENaC in pathological conditions where reduced NO bioavailability plays an essential role remains largely unexplored. Renal ischemia/reperfusion (IR) injury is characterized by vasoconstriction and sustained decrease in renal perfusion that is partially explained by a reduction in NO bioavailability. Therefore, we aimed to explore if an endothelial ENaC deficiency has an impact on the severity of renal injury induced by IR. Male mice with a specific endothelial sodium channel alpha (alphaENaC) subunit gene inactivation in the endothelium (endo-alphaENaC(KO)) and control littermates were subjected to bilateral renal ischemia of 22 min and were studied after 24 h of reperfusion. In control littermates, renal ischemia induced an increase in plasma creatinine and urea, augmented the kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin-2 (NGAL) mRNA levels, and produced severe tubular injury. The absence of endothelial alphaENaC expression prevented renal tubular injury and renal dysfunction. Moreover, endo-alphaENaC(KO) mice recovered faster from renal hypoxia after the ischemia episode as compared to littermates. In human endothelial cells, pharmacological ENaC inhibition promoted endothelial nitric oxide synthase (eNOS) coupling and activation. Altogether, these data suggest an important role for endothelial alphaENaC in kidney IR injury through improving eNOS activation and kidney perfusion, thus, preventing ischemic injury. |
