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

Objectives This study sought to determine 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) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. 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. Results Urinary sodium excretion was reduced by similar to 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 Delta FBFACh with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH4 bioactivity (less Delta FMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less Delta FMDBA and Delta FBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of Delta SBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reversed both macro-and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces "vascular protection" beyond that attributable to its BP-lowering effects. (J Am Coll Cardiol 2013;61:335-43) (C) 2013 by the American College of Cardiology Foundation