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Short-term high-salt loading effects on microvascular endothelial function in salt- resistant humans – specific role of oxidative stress and sympathovagal imbalance

Introduction and Aim: This project tested the hypothesis that suppression of renin-angiotensin system (RAS) and sympathetic activity by 7 day high-salt (HS) diet lead to endothelial and leukocyte activation and further, impaired microvascular reactivity in humans, by increasing oxidative stress. Materials and Methods: Project lasted for 54 months (April 2017-October 2021). Overall 132 young healthy individuals were included in project studies. All subjects adhered to a 7-day low-salt diet (3.5g salt/day), followed by a 7-day HS diet (~14.7g salt/day) protocol. Functional assessment of microvascular endothelial function, adrenergic system activity, body composition and fluid status, RAS activity, catecholamines concentration, biomarkers of oxidative status, pro- and anti-inflammatory cytokines, frequencies of peripheral blood lymphocytes, and biomarkers of endothelial activation were measured before and after HS diet. To specifically test the role of oxidative stress and sympathetic system activity in changes of microvascular reactivity due to the HS diet one group of subjects was supplemented with oral antioxidants during the HS diet, while the other group was subjected to a mental stress test. Results and Conclusions: 7-day HS diet suppresses RAS and impairs microvascular endothelium- dependent vasodilation in healthy individuals ; these changes are independent of blood pressure, body composition or fluid retention, but are the consequences of the unique effect of HS on endothelial function. HS diet induces oxidative disbalance, with antioxidant supplementation during HS diet preserving both oxidative status and endothelial microvascular reactivity. HS diet also suppresses sympathetic activity which represents a physiological response, rather than direct pathophysiological mechanism by which HS diet affects microvascular endothelial function in healthy individuals. HS diet induces lymphocyte activation, resulting in enhanced production of pro-inflammatory, but also anti-inflammatory cytokines, while increased oxidative stress, due to HS loading, alters immune regulatory mechanisms. Taken together, oxidative disbalance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals.

high-salt diet ; oxidative stress ; endothelium ; inflammation ; autonomic nervous system

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