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 (BH(4)) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition. RESULTS:Urinary sodium excretion was reduced by ≈ 50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMD(BA)]) and resistance (forearm blood flow responses to acetylcholine [FBF(ACh)]) artery EDD were 68% and 42% (peak FBF(ACh)) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ΔFBF(ACh) with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH(4) bioactivity (less ΔFMD(BA) with acute BH(4)), abolished tonic superoxide suppression of EDD (less ΔFMD(BA) and ΔFBF(ACh) with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ΔSBP. 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 BH(4) bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces "vascular protection" beyond that attributable to its BP-lowering effects.
RCT Entities:
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 (BH(4)) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition. RESULTS: Urinary sodium excretion was reduced by ≈ 50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMD(BA)]) and resistance (forearm blood flow responses to acetylcholine [FBF(ACh)]) artery EDD were 68% and 42% (peak FBF(ACh)) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ΔFBF(ACh) with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH(4) bioactivity (less ΔFMD(BA) with acute BH(4)), abolished tonic superoxide suppression of EDD (less ΔFMD(BA) and ΔFBF(ACh) with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ΔSBP. 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 BH(4) bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces "vascular protection" beyond that attributable to its BP-lowering effects.
Authors: Véronique L Roger; Alan S Go; Donald M Lloyd-Jones; Emelia J Benjamin; Jarett D Berry; William B Borden; Dawn M Bravata; Shifan Dai; Earl S Ford; Caroline S Fox; Heather J Fullerton; Cathleen Gillespie; Susan M Hailpern; John A Heit; Virginia J Howard; Brett M Kissela; Steven J Kittner; Daniel T Lackland; Judith H Lichtman; Lynda D Lisabeth; Diane M Makuc; Gregory M Marcus; Ariane Marelli; David B Matchar; Claudia S Moy; Dariush Mozaffarian; Michael E Mussolino; Graham Nichol; Nina P Paynter; Elsayed Z Soliman; Paul D Sorlie; Nona Sotoodehnia; Tanya N Turan; Salim S Virani; Nathan D Wong; Daniel Woo; Melanie B Turner Journal: Circulation Date: 2011-12-15 Impact factor: 29.690
Authors: D R Seals; H Tanaka; C M Clevenger; K D Monahan; M J Reiling; W R Hiatt; K P Davy; C A DeSouza Journal: J Am Coll Cardiol Date: 2001-08 Impact factor: 24.094
Authors: Ulf Landmesser; Sergey Dikalov; S Russ Price; Louise McCann; Tohru Fukai; Steven M Holland; William E Mitch; David G Harrison Journal: J Clin Invest Date: 2003-04 Impact factor: 14.808
Authors: Kristen L Jablonski; Jelena Klawitter; Michel Chonchol; Candace J Bassett; Matthew L Racine; Douglas R Seals Journal: Clin J Am Soc Nephrol Date: 2015-04-21 Impact factor: 8.237
Authors: S Lennon-Edwards; M G Ramick; E L Matthews; M S Brian; W B Farquhar; D G Edwards Journal: Nutr Metab Cardiovasc Dis Date: 2014-05-24 Impact factor: 4.222
Authors: William B Farquhar; David G Edwards; Claudine T Jurkovitz; William S Weintraub Journal: J Am Coll Cardiol Date: 2015-03-17 Impact factor: 24.094
Authors: Diana I Jalal; Emily Decker; Loni Perrenoud; Kristen L Nowak; Nina Bispham; Tapan Mehta; Gerard Smits; Zhiying You; Douglas Seals; Michel Chonchol; Richard J Johnson Journal: J Am Soc Nephrol Date: 2016-09-12 Impact factor: 10.121