Objectives: to investigate the effect of a 7 - day high-salt (HS) diet on the specific role of nitric oxide (NO) in the micro- and macrovascular response to a 7 - day salt load in healthy individuals. An additional goal is to examine the concept of non-osmotic sodium storage in the skin during 7 - day HS loadin in healthy individuals. Study design: the study was designed as a non-randomized controlled trial in which all subjects were subjected to the same experimental protocol with multiple repeated measurements. Participants and methods: 46 young healthy people of both sexes participated in the research. For the first 7 days, they were on a low-salt diet (LS) (3.5 g salt/day), then on a high-salt diet (HS) (~14.7 g salt/day). Endothelial nitric oxide-mediated vasodilatation in the microcirculation was assessed by measuring local thermal skin hyperemia (LTH) using laser Doppler flowmetry (LDF), and in the macrocirculation by measuring the flow-mediated dilation (FMD) of the brachial artery using ultrasound before HS and after the HS diet. Body fluid status was assessed using a 4 - terminal noninvasive impedance analyzer, while systemic hemodynamics and arterial blood pressure were measured using impedance cardiography (ICG). Concentrations of NO, three NOS enzyme isoforms (eNOS, iNOS and nNOS) and VEGF-C were measured before and after the HS diet. Results: the results of 24 - hour urinary sodium excretion confirmed that all participants adhered to the dietary protocol. The 7 - day HS diet significantly reduced cutaneous microvascular LTH and brachial artery FMD compared to the LS diet, independent of arterial blood pressure or changes in body fluid status. Serum eNOS concentration increased significantly, nNOS significantly decreased, while iNOS and NO remained unchanged after HS compared to LS diet. Serum VEGF-C concentration, interstitial fluid volume as well as SVRI remained unchanged after the HS diet compared to the LS diet. Conclusion: a 7 - day diet with increased salt intake causes an impairment of nitric oxide-dependent endothelial vasodilation in the microcirculation and macrocirculation of healthy individuals, independent of changes in arterial pressure. The dissociation in the response of eNOS (increase in serum level) and nNOS (decrease in serum level) to a diet with increased table salt intake indicates a complex adaptation of the main isoforms of NO-generating enzymes to HS intake in healthy individuals. Results on serum VEGF-C level, interstitial fluid volume, and SVRI in response to a 7 - day HS diet failed to support the concept of non-osmotic sodium storage in the skin, at least in terms of such short-term dietary salt modulation in healthy subjects.