Ten days of high dietary sodium does not impair cerebral blood flow regulation in healthy adults

Abstract

High dietary sodium impairs cerebral blood flow regulation in rodents and is associated with increased stroke risk in humans. However, the effects of multiple days of high dietary sodium on cerebral blood flow regulation in humans is unknown. Therefore, the purpose of this study was to determine whether ten days of high dietary sodium impairs cerebral blood flow regulation. Ten participants (3F/7M; age: 30 ± 10 years; blood pressure (BP): 113 ± 8/62 ± 9 mmHg) participated in this randomized, cross-over design study. Participants were placed on 10-day diets that included either low- (1000 mg/d), medium- (2300 mg/d) or high- (7000 mg/d) sodium separated by ≥four weeks. Urinary sodium excretion, beat-to-beat BP (finger photoplethysmography), middle cerebral artery velocity (transcranial Doppler), and end-tidal carbon dioxide (capnography) was measured. Dynamic cerebral autoregulation during a ten-minute baseline was calculated and cerebrovascular reactivity assessed by determining the percent change in middle cerebral artery blood flow velocity to hypercapnia (8% CO₂, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Urinary sodium excretion increased in a stepwise manner (ANOVA P = 0.001) from the low, to medium, to high condition. There were no differences in dynamic cerebral autoregulation between conditions. While there was a trend for a difference during cerebrovascular reactivity to hypercapnia (ANOVA P = 0.06), this trend was abolished when calculating cerebrovascular conductance (ANOVA: P = 0.28). There were no differences in cerebrovascular reactivity (ANOVA P = 0.57) or conductance (ANOVA: P = 0.73) during hypocapnia. These data suggest that ten days of a high sodium diet does not impair cerebral blood flow regulation in healthy adults.

Introduction

High dietary sodium consumption is a large contributor to strokes and cerebrovascular disease, independent of changes in resting blood pressure (BP) (Appel et al., 2011; Strazzullo et al., 2009). Strokes are the fifth leading cause of death in the United States (Stroke Facts | cdc.gov [Online], 2017) and in a meta-analysis, high dietary sodium intake resulted in a 23% increased risk of stroke (Strazzullo et al., 2009). Moreover, the Center for Disease Control and Prevention recommends lowering sodium intake as a means to reduce stroke risk (Stroke Facts | cdc.gov [Online], 2017). The American Heart Association recommends an upper limit of 2300 mg of sodium per day with an optimal level at 1500 mg of sodium per day (Sodium and Salt [Online], 2017). Despite these recommendations, nine out of ten Americans do not follow these guidelines and consume about 3600 mg of sodium per day (Dietary Guidelines for Americans 2015-2020 [Online], 2015). Thus, there is critical need to understand if high dietary sodium impairs cerebral blood flow regulation, which may precede the development of cerebrovascular disease.

The impact of high sodium intake on cerebral vessels has been studied in animal models. For example, in rodents, high sodium intake impairs the ability of the brain to maintain cerebral blood flow during decreases in systemic BP (Allen et al., 2018), indicating impaired cerebral autoregulation. High sodium feeding also attenuates flow-induced dilation of the isolated middle cerebral artery (MCA) (Cosic et al., 2016) and impairs relaxation of the MCA during hypoxia (Lombard et al., 2003) without changes in resting BP. In these rodent models, returning the animals to a low sodium diet restored vascular relaxation of the MCA to acetylcholine (McEwen et al., 2009), suggesting that high dietary sodium impaired cerebral blood flow regulation.

While our group and others (Babcock et al., 2020; DuPont et al., 2013; Lennon-Edwards et al., 2014; Matthews et al., 2015) have demonstrated that high dietary sodium impairs peripheral vasculature function in humans, less is known about the chronic impact of high dietary sodium intake on the cerebral vasculature and cerebral blood flow regulation. This is important since a reduction in cerebrovascular reactivity to hypercapnia (Markus and Cullinane, 2001) and impaired dynamic cerebral autoregulation (Castro et al., 2017) are associated with a greater risk of future strokes. Therefore, the purpose of this study was to assess dynamic cerebral autoregulation and cerebrovascular reactivity following ten days each of low- (1,000 mg/d), medium- (2300 mg/d) and high- (7000 mg/d) sodium diets separated by ≥ four weeks. We hypothesized that a high sodium diet would impair dynamic cerebral autoregulation and reduce cerebrovascular reactivity compared to the low- and medium‑sodium diets in healthy adults. Determining the effect of dietary sodium on cerebral blood flow regulation has important implications in elucidating the link between high dietary sodium consumption and increased cerebrovascular disease and stroke risk (Farahmand et al., 2013; Gardener et al., 2012).