Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB336

Poster Communications

Dietary Salt Induces Vascular Dysfunction in C57BL/6J Mice

A. Ralph1, C. Grenier1, H. M. Costello1, K. Stewart1, A. Czopek1, N. Dhaun1, M. A. Bailey1

1. University of Edinburgh, Edinburgh, United Kingdom.


Average individual salt intake is ~10g/day worldwide, exceeding the 5g/day recommended by the World Health Organisation as the upper limit tolerable to health[1]. This habitually high salt intake is associated with cardiovascular and renal disease, with the effect upon blood pressure (BP) as a pivotal factor in the development of these global health problems. The underlying mechanisms linking high salt intake to increased BP remain controversial. Impaired renal sodium (Na) excretion[2] and vasodysfunction[3] are proposed as key players in salt-induced BP rises. Here, we hypothesised that dietary salt induces endothelial dysfunction, which would be reflected in an increase in BP. We examined this in adult male C57BL/6J mice fed diets containing either 0.3% Na (n=10-15), 1.3% Na (n=7-8) or 3.0% Na (n=10-11) for 1-2 weeks. Mice were culled by decapitation and blood was collected to measure plasma aldosterone levels. Vascular reactivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was determined in dissected mesenteric arteries using wire myography. Data are mean±SEM with groups compared by one-way ANOVA with post-hoc Bonferroni testing, unless specified otherwise. Plasma aldosterone (pg/mL) was significantly suppressed by dietary salt (0.3% 68.5±5.2 vs 1.3% 30.4±5.9, P=0.0003; or vs 3% 30.9±6.4, P=0.0002), confirming normal regulation of the renin-angiotensin system here. In mesenteric arteries, sensitivity to ACh was diminished by high salt intake (Fig.1A) expressed as logIC50 (0.3% 7.189±0.195 vs 1.3% 6.054±0.120, P=0.0023), which was particularly evident in response to 3% Na (Fig.1C; 3% 6.057±0.120, P=0.0005). This reduced sensitivity was not observed with direct nitric oxide (NO) provision by SNP (Fig.1B 0.3% 6.624±0.180 vs 1.3% 6.845±0.314, P=0.936; or vs Fig.1D 3% 6.824±0.139, P=0.910). In a separate cohort (n=7) of conscious, unrestrained C57BL/6J mice, BP measurement was carried out using radiotelemetry as previously described[4]. A modest but statistically significant rise in mean BP (MBP) was noted when dietary salt content was increased from 0.3% Na (103.3±2.3mmHg) to 3% Na (114.4±2.8mmHg, P=0.0006; paired t-test). To conclude, elevating salt intake decreases mesenteric artery reactivity to ACh but not to SNP, indicating that dietary salt impairs endothelial-dependent NO production and would be likely to increase vascular tone in vivo. We also found that high salt intake increased MBP in these mice, which is supportive of the role of vasodysfunction thus far. The next steps involve evaluating renal function following salt intake and its possible contribution to the salt-induced increases in BP seen.

Where applicable, experiments conform with Society ethical requirements