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Impact of Sodium Nitrate on Measures of Vascular Function and Biomarkers of Inflammation in Patients with Peripheral Artery Disease: A Preliminary Assessment
Author(s) -
Norton Samuel L,
Ueda Kenichi,
Ganger Charles T,
Treichler David P,
Casey Darren P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.736.8
Subject(s) - medicine , reactive hyperemia , vasodilation , endothelial dysfunction , vasoconstriction , vascular resistance , nitric oxide , placebo , brachial artery , blood flow , blood pressure , forearm , endothelium , cardiology , surgery , pathology , alternative medicine
Peripheral artery disease (PAD) is associated with attenuated limb blood flow, reduced nitric oxide (NO) bioavailability, as well as elevated levels of circulating inflammatory and adhesion biomarkers. NO is a critical regulator of vascular tone and possesses several anti‐inflammatory properties. Recent evidence suggests that inorganic nitrate can be reduced to bioavailable NO in blood and various tissues. Thus, the aim of this study was to test the hypothesis that long‐term dietary nitrate supplementation in patients with PAD would 1) improve peak vasodilator capacity in resistance arteries of the arm and leg and 2) decrease plasma markers of inflammation (IL‐6) and cell adhesion (ICAM, VCAM, MCP‐1). 19 older adults with PAD (73 ± 10 yr) were randomly assigned to either 8‐weeks of daily oral sodium nitrate (NaNO 3 ; 1g) or placebo. Peak blood flow was assessed using venous occlusion plethysmography in the forearm and calf following 5 minutes of ischemia (reactive hyperemia). Peak vascular conductance (surrogate for vasodilation) was calculated as blood flow/mean arterial pressure. Plasma levels of inflammatory and cell adhesion molecules were determined utilizing commercially available enzyme‐linked immunosorbent assays (RnD Systems). Preliminary analysis (2 way repeated measures ANOVA) of 12 patients that received NaNO 3 and 7 patients that received placebo revealed no significant group × time interactions for any of the outcome measures. However, examination of only the NaNO 3 group demonstrated that peak calf blood flow (10.7 ± 1.7 vs. 12.8 ± 1.8 ml/dL of limb volume/min) and vascular conductance (10.1 ± 1.5 vs. 12.7 ± 1.8 ml/dL of limb volume/min/100mmHg) increased post treatment ( P < 0.05). Peak blood flow (P = 0.44) and vascular conductance (P= 0.45) in the arm did not change following treatment with NaNO 3 . Plasma levels of IL‐6 decreased post treatment (3.98 ± 0.64 vs. 3.49 ± 0.56 pg/ml, P < 0.05), however, NaNO 3 had no effect on any of the plasma adhesion molecules (P = 0.15 – 0.43). Our preliminary data suggest that oral NaNO 3 may provide a therapeutic benefit to vasodilator capacity in the lower extremity (i.e. diseased limb) of patients with severe PAD. Moreover, NaNO 3 may promote an anti‐inflammatory effect in this patient population. Support or Funding Information Funded by the American Heart Association 13GRNT16490002 (DPC). The Undergraduate Summer Research Fellowship program is supported by the American Physiological Society (SLN).