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 ±â€Š3.88 mm/mm; P = 0.31, following NTG; and -0.03 ±â€Š1.64 mm/mm; 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 ±â€Š1.35 and 0.84 ±â€Š1.56 mm/mm 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.