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- Title
Aldosterone synthase knockout mouse as a model for sodium-induced endothelial sodium channel up-regulation in vascular endothelium.
- Authors
Jeggle, Pia; Hofschröer, Verena; Maase, Martina; Bertog, Marko; Kusche-Vihrog, Kristina
- Abstract
Recently, a novel feedforward activation of the endothelial epithelial sodium channel (ENaC) [endothelial sodium channel (EnNaC)] by sodium was reported that counteracts ENaC function in kidney. In the absence of aldosterone, a rise in extracellular sodium (>145 mM) increases EnNaC surface abundance, thereby stiffening the cortex of vascular endothelial cells (ECs) in vitro. The latter reduces the release of NO--the hallmark of endothelial dysfunction. Here, we test whether high extracellular sodium per se increases EnNaC expression and cortical stiffness in an aldosterone synthase (Cyp11b2)-deficient (AS-/-) mouse model. Therefore, we employed in situ ECs of ex vivo aorta preparations from wild-type (WT) and AS-/-. EnNaC surface expression (-16%) and cortical stiffness (-22%) were reduced in AS-/-, compared with WT, whereas NO secretion was exclusively detectable in AS-/-. EnNaC inhibition with benzamil decreased stiffness in both, while mineralocorticoid receptor antagonism diminished stiffness only in the WT. In the absence of aldosterone, high sodium (150 mM) increased EnNaC surface expression ex vivo (plus 19%) and cortical stiffness ex vivo (plus 41%) and in vivo (plus 44%). Application of aldosterone adjusted the stiffness of AS-/- to the WT level. We conclude that high sodium per se determines EnNaC expression and consequently endothelial cortical nanomechanics, thus likely contributing to endothelial dysfunction.--Jeggle, P., Hofschröer, V., Maase, M., Bertog, M., Kusche-Vihrog, K. Aldosterone synthase knockout mouse as a model for sodium-induced endothelial sodium channel up-regulation in vascular endothelium.
- Subjects
VASCULAR endothelium; ALDOSTERONE synthesis; SODIUM channels; KNOCKOUT mice; MINERALOCORTICOID receptors; PHYSIOLOGY; DISEASES
- Publication
FASEB Journal, 2016, Vol 30, Issue 1, p45
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-259606