title: The role of ENaC in vascular endothelium.
abstract: Once upon a time, the expression of the epithelial sodium channel (ENaC) was mainly assigned to the kidneys, colon and sweat glands where it was considered to be the main determinant of sodium homeostasis. Recent, though indirect, evidence for the possible existence of ENaC in a non-epithelial tissue was derived from the observation that the vascular endothelium is a target for aldosterone. Inhibitory actions of the intracellular aldosterone receptors by spironolactone and, more directly, by ENaC blockers such as amiloride supported this view. Shortly after, direct data on the expression of ENaC in vascular endothelium could be demonstrated. There, endothelial ENaC (EnNaC) could be defined as a major regulator of cellular mechanics which is a critical parameter in differentiating between vascular function and dysfunction. Foremost, the mechanical stiffness of the endothelial cell cortex, a layer 50-200 nm beneath the plasma membrane, has been shown to play a crucial role as it controls the production of the endothelium-derived vasodilator nitric oxide (NO) which directly affects the tone of the vascular smooth muscle cells. In contrast to soft endothelial cells, stiff endothelial cells release reduced amounts of NO, the hallmark of endothelial dysfunction. Thus, the combination of endothelial stiffness and myogenic tone might increase the peripheral vascular resistance. An elevation of arterial blood pressure is supposed to be the consequence of such functional changes. In this review, EnNaC is discussed as an aldosterone-regulated plasma membrane protein of the vascular endothelium that could significantly contribute to maintaining of an appropriate arterial blood pressure but, if overexpressed, could participate in the pathogenesis of arterial hypertension.
authors.affiliation: Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany, kusche@uni-muenster.de.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.forename: Pia
authors.initials: P
authors.lastname: Jeggle
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D019276:Glycocalyx / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D009569:Nitric Oxide
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