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Peripheral artery disease (PAD) is characterized by functional and vascular impairments as well as elevated levels of inflammation which are associated with reduced nitric oxide (NO) bioavailability. Inorganic nitrate supplementation boosts NO bioavailability potentially improving functional and vasodilatory capacities and may reduce inflammation. Twenty-one patients with PAD were randomly assigned to sodium nitrate (NaNO 3 ) or placebo supplementation groups for eight-weeks. Outcome measures included a 6-min walk test (6 MWT), blood flow and vasodilator function in the forearm and calf, as well as plasma inflammatory and adhesion biomarker concentrations. NaNO 3 elevated plasma nitrate (32.3 ± 20.0 to 379.8 ± 204.6 μM) and nitrite (192.2 ± 51.8 to 353.1 ± 134.2 nM), improved 6 MWT performance (387 ± 90 to 425 ± 82 m), peak calf blood flow (BF Peak ; 11.6 ± 4.9 to 14.1 ± 5.1 mL/dL tissue/min), and peak calf vascular conductance (VC Peak ; 11.1 ± 4.3 to 14.2 ± 4.9 mL/dL tissue/min/mmHg) (p < 0.05 for all). Improvements in calf BF Peak (r = 0.70, p < 0.05) and VC Peak (r = 0.61, p < 0.05) correlated with changes in 6 MWT distance. Placebo supplementation did not change plasma nitrate or nitrite, 6 MWT, calf BF Peak , or calf VC Peak . Forearm vascular function nor inflammatory and adhesion biomarker concentrations changed in either group. Eight-weeks of NaNO 3 supplementation improves vasodilatory capacity in the lower-limbs of patients with PAD, which correlated with improvement in functional capacity., (Copyright © 2018. Published by Elsevier Inc.)

The vasoactive molecule nitric oxide (NO) contributes to regulation of blood pressure (BP) at rest and during exercise. Age-related exaggerated increased BP responses during exercise have been proposed to be due in part to a decreased NO bioavailability and possibly an enhanced skeletal muscle metaboreflex. In the present study we sought to determine if age-related differences in BP responses to skeletal muscle metaboreflex activation exist. Additionally, since NO bioavailability can be improved with exogenous nitrate (NO 3 ) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO - ) via the nitrate-nitrite-NO pathway, we tested the hypothesis that inorganic NO 3 - supplementation would reduce BP responses to muscle metaboreflex activation in healthy older adults. 13 older adults (67 ± 1 years) participated in a randomized, double-blind, placebo controlled crossover study consisting of four weeks of NO 3 - supplementation [beetroot powder; 250 mg (∼4.03 mmol) of NO 3 - and 20 mg (∼0.29 mmol) of NO 2 - ] and four weeks of placebo (beetroot powder devoid of NO 3 - /NO 2 - ). Skeletal muscle metaboreflex testing consisted of isometric handgrip exercise (IHG) at 30% of maximal voluntary contraction immediately followed by post exercise forearm ischemia (PEI), which was achieved by inflation of a rapid pressure cuff (240 mmHg) around the upper arm. BP responses were analyzed as the change (Δ) from baseline to the end of IHG and PEI. An additional 10 young adults (25 ± 1 years) were recruited to serve as a reference cohort and address if BP responses to skeletal muscle metaboreflex activation were greater with aging. BP responses to IHG were similar between the young and older adults. However, older adults demonstrated a greater increase in systolic BP during PEI (P < 0.05). Plasma NO 3 - and NO 2 - were increased following NO 3 - supplementation in older adults (P < 0.01). ΔSystolic BP (19 ± 2 vs. 13±3 mmHg, P < 0.05), ΔDiastolic BP (7 ± 1 vs. 5±1 mmHg, P < 0.05) and ΔMean arterial pressure (11 ± 1 vs. 8±2 mmHg, P < 0.05) were reduced during PEI following four weeks of NO 3 - supplementation, whereas placebo had no effect on ΔSystolic BP (16 ± 2 vs. 17±2 mmHg), ΔDiastolic BP (5 ± 1 vs. 7±1 mmHg), and ΔMean arterial pressure (8 ± 1 vs. 10±1 mmHg) during PEI (all P > 0.05). These data suggest that inorganic NO 3 - supplementation attenuates skeletal muscle metaboreflex mediated increases in BP during exercise in older adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Aging is associated with elevated blood pressure (peripheral and aortic; BP) and aortic augmentation index (AIx) which may contribute to aortic BP. Although inorganic nitrate consumption reduces peripheral BP in both young and older adults, the effects of nitrate consumption on aortic BP and wave reflection in young and older adults is unknown. Therefore, we sought to characterize the effects of nitrate consumption on aortic BP and AIx in young and older adults., Methods: Noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and following (60, 90, 120, 150, and 180 min) consumption of a nitrate-rich beetroot juice in 26 healthy adults (young: 25 ± 4 years, n = 14; older: 64 ± 5 years, n = 12). Aortic BP and indices of aortic wave reflection (AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform., Results: Nitrate consumption increased plasma nitrite in both groups 60-180 min following beetroot consumption (P < 0.001). Nitrate consumption reduced peripheral and aortic BP in both young and older adults (P < 0.05), with the change being similar between age groups. Conversely, indices of aortic wave reflection were reduced only in young adults following nitrate consumption (range of change from baseline over time: AIx@75bpm, -4.3 to -8.8%, P < 0.05), whereas aortic AIx remained unchanged in the older adults., Conclusions: Taken together, our results suggest that acute dietary nitrate supplementation reduces peripheral and aortic BP similarly in young and older adults despite differential effects on aortic AIx between age groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown., Purpose: Investigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia., Methods: 20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m(-2)) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio., Results: Aortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05)., Conclusions: Acute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia., (Copyright © 2015 Elsevier Inc. All rights reserved.)