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The role of ENaC in vascular endothelium

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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.

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Acknowledgments

This work was supported by grants from the Deutsche Forschungsgemeinschaft (Koselleck-OB 63/18, KU 1496/7-1), the ‘Innovative Medical Research’ of the University of Muenster Medical School (KU 120808) and the Else-Kröner-Fresenius Stiftung (2010 A116).

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  1. Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany

    Kristina Kusche-Vihrog, Pia Jeggle & Hans Oberleithner

  2. Department of Pharmacology, University of Cambridge, Cambridge, CB2 1PD, UK

    Pia Jeggle

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  1. Kristina Kusche-Vihrog
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Correspondence to Kristina Kusche-Vihrog.

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Kusche-Vihrog, K., Jeggle, P. & Oberleithner, H. The role of ENaC in vascular endothelium. Pflugers Arch - Eur J Physiol 466, 851–859 (2014). https://doi.org/10.1007/s00424-013-1356-3

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