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Salt controls endothelial and vascular phenotype

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Abstract

High salt (NaCl) intake promotes the development of vascular diseases independent of a rise in blood pressure, whereas reduction of salt consumption has beneficial effects for the arterial system. This article summarizes our current understanding of the molecular mechanisms of high salt-induced alterations of the endothelial phenotype, the impact of the individual endothelial genotype, and the overall vascular phenotype. We focus on the endothelial Na+ channel (EnNaC)-controlled nanomechanical properties of the endothelium, since high Na+ leads to an EnNaC-induced Na+-influx and subsequent stiffening of endothelial cells. The mechanical stiffness of the endothelial cell (i.e., the endothelial phenotype) plays 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. This endothelium-born process is followed by the development of arterial stiffness (i.e., the vascular phenotype), predicting the development of vascular end-organ damage such as myocardial infarction, stroke, and renal impairment. In this context, we outline the potential clinical implication of direct (amiloride) and indirect (spironolactone) EnNaC inhibition on vascular function. However, interindividual differences exist in the response to high salt intake which involves different endothelial genotypes. Thus, selected genes and genetic variants contributing to the development of salt-induced endothelial dysfunction and hypertension are discussed. In this review, we focus on the role of salt in endothelial and vascular (dys)function and the link between salt-induced changes of the endothelial and vascular phenotype and its clinical implications.

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Acknowledgments

This work was supported by grants of the Deutsche Forschungsgemeinschaft (Koselleck OB 63/18, KU 1496/7-1), the Else-Kröner-Fresenius Stiftung (2010_A116), “Innovative Medical Research” (IMF) of the University of Münster (KU 120808), and by the Centre of Excellence (Cells in Motion; CIM), University of Münster. EB was supported by a Heisenberg professorship from the Deutsche Forschungsgemeinschaft (Br1589/8-2). The authors would also thank COST Action TD1002 and COST Action BM 1301 for supporting their networking activities.

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

    Kristina Kusche-Vihrog

  2. Institute of Sports Medicine, Molecular Genetics of Cardiovascular Disease, University Hospital Muenster, Muenster, Germany

    Boris Schmitz

  3. Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Muenster, Germany

    Eva Brand

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  1. Kristina Kusche-Vihrog
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Kusche-Vihrog, K., Schmitz, B. & Brand, E. Salt controls endothelial and vascular phenotype. Pflugers Arch - Eur J Physiol 467, 499–512 (2015). https://doi.org/10.1007/s00424-014-1657-1

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