We have previously demonstrated that aging reduces the compensatory vasodilator response during hypoxic exercise due to blunted nitric oxide (NO) signaling. Recent evidence suggests that NO bioavailability can be augmented by dietary nitrate through the nitrate-nitrite pathway. Thus we tested the hypothesis that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise, particularly in older adults. Thirteen young (25 ± 1 yr) and 12 older (64 ± 2 yr) adults performed rhythmic forearm exercise at 20% of maximum voluntary contraction during normoxia and hypoxia (∼80% O2 saturation); both before (control) and 3 h after beetroot juice (BR) consumption. Forearm vascular conductance (FVC; ml·min(-1)·100 mmHg(-1)) was calculated from forearm blood flow (ml/min) and blood pressure (mmHg). Compensatory vasodilation was defined as the relative increase in FVC due to hypoxic exercise (i.e., % increase compared with respective normoxic exercise trial). Plasma nitrite was determined from venous blood samples obtained before the control trials and each of the exercise trials (normoxia and hypoxia) after BR. Consumption of BR increased plasma nitrite in both young and older adults (P < 0.001). During the control condition, the compensatory vasodilator response to hypoxic exercise was attenuated in older compared with young adults (3.8 ± 1.7% vs. 14.2 ± 1.2%, P < 0.001). Following BR consumption, compensatory vasodilation did not change in young (13.7 ± 3.3%, P = 0.81) adults but was substantially augmented in older adults (11.4 ± 2.1%, P < 0.01). Our data suggest that acute dietary nitrate supplementation increases the compensatory vasodilator response to hypoxic exercise in older but not young adults.

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The influence of aging on contraction-induced rapid vasodilation has been well characterized in the forearm. We sought to examine the impact of aging on contraction-induced rapid vasodilation in the leg following single muscle contractions and determine whether potential age-related impairments were similar between limbs (leg vs. arm). Fourteen young (23 ± 1 years) and 16 older (66 ± 1 years) adults performed single leg knee extensions at 20%, 40%, and 60% of work rate maximum. Femoral artery diameter and blood velocity were measured using Doppler ultrasound. Limb vascular conductance (VC) was calculated using blood flow (mL·min−1) and mean arterial pressure (mmHg). Peak and total vasodilator responses in the leg (change [Δ] in VC from baseline) were blunted in older adults by 44–50% across exercise intensities (P < 0.05 for all). When normalized for muscle mass, age-related differences were still evident (P < 0.05). Comparing the rapid vasodilator responses between the arm and the leg of the same individuals at similar relative intensities (20% and 40%) reveals that aging influences peak and total vasodilation equally between the limbs (no significant age × limb interaction at either intensity, P = 0.28–0.80). Our data demonstrate that (1) older adults exhibit an attenuated rapid hyperemic and vasodilator response in the leg; and (2) the age-related reductions in rapid vasodilation are similar between the arm and the leg. The mechanisms contributing to the age-related differences in contraction-induced rapid vasodilation are perhaps similar to those seen with the forearm model, but have not been confirmed.

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) 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 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; 11.6 ± 4.9 to 14.1 ± 5.1 mL/dL tissue/min), and peak calf vascular conductance (VC; 11.1 ± 4.3 to 14.2 ± 4.9 mL/dL tissue/min/mmHg) (p < 0.05 for all). Improvements in calf BF (r = 0.70, p < 0.05) and VC (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, or calf VC. Forearm vascular function nor inflammatory and adhesion biomarker concentrations changed in either group. Eight-weeks of NaNO supplementation improves vasodilatory capacity in the lower-limbs of patients with PAD, which correlated with improvement in functional capacity.

Inorganic nitrate supplementation reduces peripheral blood pressure (BP) in several human populations. We examined whether acute nitrate supplementation decreases central aortic pressures and indices of wave reflection in young and older adults. In 13 young (25±1 yr, 10M/3F) and 12 older (64 ± 1yr, 9M/3F) normotensive adults, 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 (BR). Aortic BP and indices of aortic wave reflection (Augmentation Index; AIx and AIx normalized for heart rate; AIx@75bpm) were calculated from the generated aortic pressure waveform. Plasma nitrite concentration increased in both groups 60‐180 min following BR (P<0.001). Peripheral (Systolic: ~5mmHg; Diastolic: ~4mmHg) and aortic BP (Systolic: ~6mmHg; Diastolic: ~4mmHg) were reduced 90‐180min post BR in older (P<0.05), but not young adults. Conversely, AIx (3±3 vs ‐5±3%) and AIx@75bpm (‐6±3 vs ‐15±3%) were reduced in young adults 180 min post BR (P<0.05 for both). Whereas, AIx (28±3 vs 28±2%, P=1.0) and AIx@75bpm (21±3 vs 20±3%, P=0.99) did not change in the older adults. Our data suggest that acute dietary nitrate supplementation reduces central aortic BP in older adults, despite not altering indices of aortic wave reflection.Supported by ACSM Foundation