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Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, Vascular Endothelial Growth Factor C, and Blood Pressure.

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Selvarajah, Viknesh 
Mäki-Petäjä, Kaisa M 
Pedro, Liliana 
Bruggraber, Sylvaine FA 
Burling, Keith 


High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that dietary salt loading results in dermal Na+ accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise in BP. Our objective was to determine whether these mechanisms function in humans. We assessed skin electrolytes, BP, and plasma VEGF-C in 48 healthy participants randomized to placebo (70 mmol sodium/d) and slow sodium (200 mmol/d) for 7 days. Skin Na+ and K+ concentrations were measured in mg/g of wet tissue and expressed as the ratio Na+:K+ to correct for variability in sample hydration. Skin Na+:K+ increased between placebo and slow sodium phases (2.91±0.08 versus 3.12±0.09; P=0.01). In post hoc analysis, there was a suggestion of a sex-specific effect, with a significant increase in skin Na+:K+ in men (2.59±0.09 versus 2.88±0.12; P=0.008) but not women (3.23±0.10 versus 3.36±0.12; P=0.31). Women showed a significant increase in 24-hour mean BP with salt loading (93±1 versus 91±1 mm Hg; P<0.001) while men did not (96±2 versus 96±2 mm Hg; P=0.91). Skin Na+:K+ correlated with BP, stroke volume, and peripheral vascular resistance in men but not in women. No change was noted in plasma VEGF-C. These findings suggest that the skin may buffer dietary Na+, reducing the hemodynamic consequences of increased salt, and this may be influenced by sex.



blood pressure, skin, sodium, stroke volume, vascular endothelial growth factor C, Adult, Blood Pressure, Diet, Sodium-Restricted, Double-Blind Method, England, Female, Hemodynamics, Humans, Hypertension, Male, Middle Aged, Potassium, Renal Elimination, Sex Factors, Skin, Sodium, Sodium Chloride, Vascular Endothelial Growth Factor C, Water-Electrolyte Balance

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British Heart Foundation (None)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10093)
NIHR Clinical Research Network Eastern (via Cambridge University Hospitals NHS Foundation Trust (CUH)) (CRN 2017/18)