Dietary Sodium Restriction Reverses Vascular Endothelial Dysfunction in Middle-Aged/Older Adults With Moderately Elevated Systolic Blood Pressure

Study Questions:

What is the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130-159 mm Hg)?

Methods:

Seventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a randomized crossover study of 4 weeks of both low (DSR) and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition. Changes in EDD in response to DSR (DSR vs. normal sodium condition) were analyzed using a series of linear mixed-effects models.

Results:

Urinary sodium excretion was reduced by approximately 50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ∆FBFACh with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH4 bioactivity (less ∆FMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ∆FMDBA and ∆ACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ∆SBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged.

Conclusions:

The authors concluded that DSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress.

Perspective:

The current study reports that restricting dietary sodium intake to a level consistent with the DASH diet improves both conduit artery (macrovascular) and resistance vessel (microvascular) endothelial function in middle-aged/older adults with moderately elevated SBP, a large clinical demographic with significant cardiovascular disease risk burden. Furthermore, it provides insight regarding the physiological mechanisms mediating improvements in vascular endothelial function with DSR, which include increased NO, and BH4 bioavailability and reduced oxidative stress. Overall, the findings support the concept that maintaining low dietary sodium intake exerts vasculoprotective effects beyond those attributable to only BP lowering, and has the potential to improve cardiovascular health and outcomes.

Keywords: Cross-Over Studies, Brachial Artery, Food Habits, Oxidative Stress, Blood Pressure, Superoxide Dismutase, Hyponatremia, Diet, Sodium-Restricted, Cardiovascular Diseases, Energy Metabolism, Diet, Hypertension


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