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Open AccessArticle

The Absence of Endothelial Sodium Channel α (αENaC) Reduces Renal Ischemia/Reperfusion Injury

1
Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, F-75006 Paris, France
2
Laboratorio de Fisiología Cardiovascular y Trasplante Renal, Unidad de Medicina Translacional, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 04510, Mexico
3
Departamento de Fisiología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico
4
INSERM U1116, Clinical Investigation Centre, Lorraine University, 54052 Vandoeuvre-lès-Nancy, France
5
INI-CRCT (Cardiovascular and Renal Clinical Trialists) F-CRIN Network, 31059 Nancy, France
*
Authors to whom correspondence should be addressed.
Contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3132; https://doi.org/10.3390/ijms20133132
Received: 4 June 2019 / Accepted: 18 June 2019 / Published: 27 June 2019
(This article belongs to the Special Issue Kidney Injury: From Molecular Basis to Therapies 2.0)
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 α (αENaC) subunit gene inactivation in the endothelium (endo-αENaCKO) 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 αENaC expression prevented renal tubular injury and renal dysfunction. Moreover, endo-αENaCKO 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 αENaC in kidney IR injury through improving eNOS activation and kidney perfusion, thus, preventing ischemic injury. View Full-Text
Keywords: ENaC; endothelium; endothelial cell stiffness; acute kidney injury; endothelial nitric oxide synthase ENaC; endothelium; endothelial cell stiffness; acute kidney injury; endothelial nitric oxide synthase
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Tarjus, A.; González-Rivas, C.; Amador-Martínez, I.; Bonnard, B.; López-Marure, R.; Jaisser, F.; Barrera-Chimal, J. The Absence of Endothelial Sodium Channel α (αENaC) Reduces Renal Ischemia/Reperfusion Injury. Int. J. Mol. Sci. 2019, 20, 3132.

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