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

Abstract

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 impairs cutaneous microvascular function independent of BP in normotensive adults and suggest a role for oxidative stress.

Figure 1. Schematic representation of local heating protocol

After resolution of the initial insertion hyperaemia, a standard non-painful local heating protocol was employed. Microdialysis sites were perfused with either lactated Ringer solution or AA for baseline measurements at 33°C. Thereafter, the local heater temperature was increased to 42°C. Upon attaining a stable plateau in red blood cell flux, l-NAME was perfused in both microdialysis sites to quantify NO-dependent vasodilatation. Following a new post-heating l-NAME stabilization, local heaters were set to 43°C and SNP was perfused to induce maximal cutaneous vasodilatation. l-NAME, N^G-nitro-l-arginine methyl ester; SNP, sodium nitroprusside.

Figure 2. Maximal cutaneous vascular conductance

Percentage of maximal cutaneous vascular conductance (%CVCmax) in the microdialysis site perfused with Ringer solution during the low-sodium (LS; filled bars) and high-sodium (HS; open bars) diets during baseline, the initial peak, NO-mediated plateau and post-heating l-NAME plateau (A). The HS diet attenuated the plateau%CVCmax compared with LS. Percentage of maximal cutaneous vascular conductance (%CVCmax) in the Ringer (open bars) and ascorbic acid (AA; hatched bars) sites during the high-sodium (HS) diet during baseline, the initial peak, NO-mediated plateau and post-heating l-NAME plateau (B). During the HS diet, AA augmented the plateau%CVCmax compared with Ringer solution. Values are mean ± SEM. *P < 0.05 vs. LS; †P<0.05 v. Ringer.

Figure 3. The NO contribution to the plateau during the HS diet in the Ringer (open bar) and ascorbic acid (AA; hatched bar) sites

AA restored the NO contribution to the plateau during the HS diet. Values are mean ± SEM. *P < 0.05 vs. Ringer solution.