Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress

Key points • Pre‐clinical studies suggest that acute dietary sodium loading impairs vascular function without alterations in blood pressure; however, human data are lacking. • In this study, normotensive salt‐resistant adults participated in a controlled feeding study, in which they consumed a low‐sodium diet for 1 week and a high‐sodium diet for 1 week, in random order. During each diet, microvascular function was assessed. • Here we report the novel finding of sodium‐induced impairments in microvascular function independent of blood pressure in healthy adults. • We additionally show that function was improved by the administration of the anti‐oxidant ascorbic acid. • Therefore, in addition to its well‐known importance for blood pressure control, lowering sodium intake may have beneficial effects on microvascular function in healthy normotensive adults. Animal studies have reported dietary salt‐induced reductions in vascular function independent of increases in blood pressure (BP). The purpose of this study was to determine if short‐term dietary sodium loading impairs cutaneous microvascular function in normotensive adults with salt resistance. Following a control run‐in diet, 12 normotensive adults (31 ± 2 years) were randomized to a 7 day low‐sodium (LS; 20 mmol day−1) and 7 day high‐sodium (HS; 350 mmol day−1) diet (controlled feeding study). Salt resistance, defined as a ≤5 mmHg change in 24 h mean BP determined while on the LS and HS diets, was confirmed in all subjects undergoing study (LS: 84 ± 1 mmHg vs. HS: 85 ± 2 mmHg; P > 0.05). On the last day of each diet, subjects were instrumented with two microdialysis fibres for the local delivery of Ringer solution and 20 mm ascorbic acid (AA). Laser Doppler flowmetry was used to measure red blood cell flux during local heating‐induced vasodilatation (42°C). After the established plateau, 10 mm l‐NAME was perfused to quantify NO‐dependent vasodilatation. All data were expressed as a percentage of maximal cutaneous vascular conductance (CVC) at each site (28 mm sodium nitroprusside; 43°C). Sodium excretion increased during the HS diet (P < 0.05). The plateau % CVCmax was reduced during HS (LS: 93 ± 1 % CVCmax vs. HS: 80 ± 2 % CVCmax; P < 0.05). During the HS diet, AA improved the plateau % CVCmax (Ringer: 80 ± 2 % CVCmax vs. AA: 89 ± 3 % CVCmax; P < 0.05) and restored the NO contribution (Ringer: 44 ± 3 % CVCmax vs. AA: 59 ± 6 % CVCmax; P < 0.05). These data demonstrate that dietary sodium loading