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

Cardiovascular diseases [CVD] remain the leading cause of death in the United States and risk of CVD increases progressively with age (1). Vascular endothelial dysfunction, as reflected by impaired endothelium-dependent dilation [EDD] of conduit arteries and/or resistance vessels (2), is a predictor of future CVD and CV events (3,4). EDD is reduced in middle-aged and older adults in the absence of major risk factors or clinical CVD (5). Systolic blood pressure [SBP] also increases with advancing age (6), resulting in ~65% of adults 50 years of age and older with SBP ≥130 mmHg (7). Importantly, the age-associated impairment of EDD is even greater in middle-aged and older adults with elevated compared with normal SBP (2,8). Dietary sodium restriction is a commonly recommended lifestyle modification for reducing risk of CVD (9). Based on recent analyses, the projected health and societal benefits resulting from population-wide dietary sodium restriction would be substantial (10). To date, such projections have focused on the effects of sodium restriction on BP. However, high dietary sodium intake has adverse cardiovascular effects independent of BP (11,12). Evidence from animal models and acute salt loading or cross-sectional observations in humans suggests a negative association between sodium intake and vascular endothelial function (11,13–16). However, presently it is unknown if dietary sodium restriction can reverse endothelial dysfunction in the common clinical setting of aging and elevated SBP. The physiological mechanisms by which dietary sodium restriction may improve vascular endothelial function in humans also are unknown. Available data from rodent models suggest that high sodium diets may impair EDD by reducing nitric oxide [NO] bioavailability as a result of oxidative stress (14,17). This may be mediated via oxidation and reduced bioavailability of tetrahydrobiopterin [BH4] (18), an essential cofactor for endothelial nitric oxide synthase [eNOS]-mediated NO production, which causes uncoupling of the enzyme (14,18). Limited data in rodents suggest that high sodium also may reduce expression of eNOS (19) and suppress the activity of superoxide dismutase [SOD], an important antioxidant enzyme (20). The aim of this study was to determine if dietary sodium restriction improves vascular endothelial dysfunction in middle-aged/older adults with moderately elevated SBP by increasing NO and BH4 bioavailability and reducing oxidative stress.