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

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.