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      Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

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          Abstract

          Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in nonosmotic storage of salt. These new concepts emphasize that sodium homeostasis and salt sensitivity seem to be related not only to the kidney malfunction but also to the endothelial dysfunction. Further investigations will be needed to assess the extent to which changes in the sodium buffering capacity of the skin interstitium and develop the treatment strategy for modulating the endothelial dysfunction.

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          Most cited references 51

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          Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States.

          Geographic variations in cardiovascular disease (CVD) and associated risk factors have been recognized worldwide. However, little attention has been directed to potential differences in hypertension between Europe and North America. To determine whether higher blood pressure (BP) levels and hypertension are more prevalent in Europe than in the United States and Canada. Sample surveys that were national in scope and conducted in the 1990s were identified in Germany, Finland, Sweden, England, Spain, Italy, Canada, and the United States. Collaborating investigators provided tabular data in a consistent format by age and sex for persons at least 35 years of age. Population registries were the main basis for sampling. Survey sizes ranged from 1800 to 23 100, with response rates of 61% to 87.5%. The data were analyzed to provide age-specific and age-adjusted estimates of BP and hypertension prevalence by country and region (eg, European vs North American). Blood pressure levels and prevalence of hypertension in Europe, the United States, and Canada. Average BP was 136/83 mm Hg in the European countries and 127/77 mm Hg in Canada and the United States among men and women combined who were 35 to 74 years of age. This difference already existed among younger persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm Hg and 115/75 mm Hg, respectively), and the slope with age was steeper in the European countries. For all age groups, BP measurements were lowest in the United States and highest in Germany. The age- and sex-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries at the 140/90 mm Hg threshold. The findings for men and women by region were similar. Hypertension prevalence was strongly correlated with stroke mortality (r = 0.78) and more modestly with total CVD (r = 0.44). Despite extensive research on geographic patterns of CVD, the 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated. The implication of this finding for national prevention strategies should be vigorously explored.
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            Molecular mechanisms of human hypertension.

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              Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group.

              The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.
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                Author and article information

                Journal
                Electrolyte Blood Press
                Electrolyte Blood Press
                EBP
                Electrolytes & Blood Pressure : E & BP
                The Korean Society of Electrolyte Metabolism
                1738-5997
                2092-9935
                June 2015
                30 June 2015
                : 13
                : 1
                : 7-16
                Affiliations
                Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                Author notes
                Corresponding Author: Sung Kyu Ha, M.D., Ph.D. Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-Gu, Seoul 135-720, Korea. Tel: +82-2-2019-3313, Fax: +82-2-3463-3882, hask1951@ 123456yuhs.ac
                Article
                10.5049/EBP.2015.13.1.7
                4520886
                Copyright © 2015 The Korean Society of Electrolyte Metabolism

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review

                Cardiovascular Medicine

                endothelial dysfunction, kidney malfunction, hypertension, sensitivity, salt

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