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      Vascular Glycocalyx Sodium Store - Determinant of Salt Sensitivity?

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          Abstract

          Smart mechanisms allow frictionless slipping of rather rigid erythrocytes (red blood cells, RBC) through narrow blood vessels. Nature solved this problem in an elegant way coating the moving object (RBC) and the tunnel wall (endothelium) by negative charges (glycocalyx). As long as these surfaces are intact, repulsive forces create a ‘security zone' that keeps the respective surfaces separated from each other. However, damage of either one of these surfaces causes loss of negative charges, allowing an unfavorable physical interaction between the RBC and the endothelium. It has been recently shown that any alteration of the endothelial glycocalyx leaves nasty footprints on the RBC glycocalyx. In this scenario, sodium ions hold a prominent role. Plasma sodium is stored in the glycocalyx partially neutralizing the negative surface charges. A ‘good' glycocalyx has a high sodium store capacity but still maintains sufficient surface negativity at normal plasma sodium. A ‘bad' glycocalyx shows the opposite. This concept was used for the development of the so-called ‘salt blood test' (SBT) that quantitatively measures RBC sodium store capacity of the glycocalyx and thus indirectly evaluates the quality of the inner vessel wall. In an initial step, the applicability of the SBT was tested in eight different medical facilities. The study shows that an increased salt sensitivity, as measured by the SBT, is more frequently found in individuals with a hypertensive history, despite antihypertensive medication. Taken together, preservation of the endothelial glycocalyx appears to be of utmost importance for maintaining a well-balanced function of the vascular system.

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          Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.

          Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.
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            Plasma sodium stiffens vascular endothelium and reduces nitric oxide release.

            Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.
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              Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells.

              Sodium transport in the distal nephron is mediated by epithelial sodium channel activity. Proteolytic processing of external domains and inhibition with increased sodium concentrations are important regulatory features of epithelial sodium channel complexes expressed in the distal nephron. By contrast, sodium channels expressed in the vascular system are activated by increased external sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. The synergistic effects, and complementary regulation, of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and probably reflect sequential evolution of the two systems. The integration of vascular tone, renal perfusion and regulation of renal sodium reabsorption is the central underpinning of the Guytonian model. In this Review, we focus on the expression and regulation of sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2015
                May 2015
                20 January 2015
                : 39
                : 1-3
                : 7-10
                Affiliations
                Institute of Physiology II, Medical Faculty, University Münster, Münster, Germany
                Author notes
                *Hans Oberleithner, MD, Institut für Physiologie II, Robert-Koch-Strasse 27b, DE-48149 Münster (Germany), E-Mail oberlei@uni-muenster.de
                Article
                368922 Blood Purif 2015;39:7-10
                10.1159/000368922
                25659848
                1c04729b-75c3-4f8a-8ffa-4250975eb2c0
                © 2015 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 3, References: 15, Pages: 4
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Heparan sulfate,Hypertension,Endothelial dysfunction,Erythrocyte shedding,Salt blood test

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