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High-salt intake affects sublingual microcirculation and is linked to body weight change in healthy volunteers

a randomized cross-over trial

Rorije, Nienke M.G.a,*; Rademaker, Emmaa,*; Schrooten, Esmee M.a; Wouda, Rosa D.a; Homan Van Der Heide, Jacob J.a; Van Den Born, Bert-Jan H.b; Vogt, Lifferta

doi: 10.1097/HJH.0000000000002015

Background: The pathophysiology of salt-sensitive hypertension remains uncertain, but may involve microvascular alterations. High-salt intake decreases microvascular density in hypertensive patients, but due to lack of studies in normotensive patients the causal pathway remains unclear. We studied whether high-salt intake decreases sublingual microvascular density in normotensive individuals and assessed the influence of body weight on changes in microvascular density.

Methods: In an open label randomized cross-over trial 18 healthy men were included to study the effect of a 2-week high-salt (>12 g/day) and low-salt (<3 g/day) diet on microvascular (diameter <20 μm) density with sublingual sidestream darkfield imaging. We used sublingual nitroglycerin (NTG) to recruit microvessels.

Results: There was no significant difference in microvascular density between diets (0.96 ± 3.88 mm/mm2; P = 0.31, following NTG; and −0.03 ± 1.64 mm/mm2; P = 0.95, without NTG). Increased salt intake was correlated with a decrease in microvascular density following NTG (r = −0.47; P = 0.047), but not without NTG (r = 0.06; P = 0.800). The decrease in microvascular density following high-salt intake was significantly larger for those with a large change in body weight as compared with those with a small changer in body weight (−0.79 ± 1.35 and 0.84 ± 1.56 mm/mm2 respectively, P = 0.031).

Conclusion: We demonstrate in healthy volunteers that higher salt intake is correlated with decreased sublingual microvascular density following administration of NTG and; larger changes in body weight following high-salt intake coincide with a larger decrease in microvascular density. Changes in microvascular density occurred without blood pressure effects, indicating that high-salt load as such contributes to microvascular changes, and may precede hypertension development.

aSection Nephrology

bSection Vascular Medicine, Department of Internal Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Correspondence to Liffert Vogt, MD, PhD, Section of Nephrology, Department of Internal Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, Meibergdreef 9, Room F4-215, 1105 AZ Amsterdam, The Netherlands. E-mail:

Abbreviations: AVA, automated vessel analysis; BP, blood pressure; CO, cardiac output; ECFV, extracellular fluid volume; HSD, high-salt diet (>12 g/day); IDF, incident dark field imaging; LSD, low-salt diet (<3 g/day); NO, nitric oxide; NTG, nitroglycerin; PPV, proportion of perfused vessels; PVDsmall, perfused vessel density diameter <20 μm; SDF, sidestream dark-field; SVR, systemic vascular resistance; TVDsmall, total vessel density diameter <20 μm

Received 18 September, 2018

Accepted 7 November, 2018

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