Inorganic nitrate supplementation enhances functional capacity and lower-limb microvascular reactivity in patients with peripheral artery disease

Abstract

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.

Coronary microvascular dysfunction is associated with exertional haemodynamic abnormalities in patients with heart failure with preserved ejection fraction

“…There is no established treatment for HFpEF that reduces mortality, and while several trials have been done, most have been negative when assessing the same therapies used in HFrEF. Furthermore, few treatments that have been looked at for the treatment of HFpEF were also studied as a possible treatment for CMD, such as inorganic nitrite and phosphodiesterase inhibitors, 25–28 but these studies were also largely negative and provided no benefit. All this indicates that there is a possible confounding effect of CMD in patients with HFpEF that should be taken into account in future studies of HFpEF treatment.…”

A Single Dose of Beetroot Juice Does Not Change Blood Pressure Response Mediated by Acute Aerobic Exercise in Hypertensive Postmenopausal Women

“…Several other interventions assessing effects of BJ intake have been completed with different populations. Previous studies have investigated chronic [7,8,9,10,11,12,28] and acute BJ ingestion [16,20,28,29,30], in athletes [17,18,19], in healthy non-athletes [31,32], and in patients in disease states [7,8,9,10,11,12,16,20]. BJ consumption has been analyzed combined with exercise [28,33] and without exercise [34].…”

“…The NO 2 − is then released into the systemic circulation for subsequent NO production [6], leading to improvements in hemodynamic regulation. Therefore, consumption of foods rich in NO 3 − may be a good strategy to improve BP regulation in target populations with an increased incidence of cardiometabolic diseases, especially when associated with exercise [7,8,9,10,11,12], since these two pathways of NO production can complement each other [6].…”

Acute Dietary Nitrate Supplementation Improves Flow Mediated Dilatation of the Superficial Femoral Artery in Healthy Older Males

“…Another possible explanation for the null findings is that these two studies included participants who had been diagnosed with peripheral arterial disease [23] and type II diabetes [68]. Low brachial FMD is a sub-clinical marker for cardiovascular disease risk [32,34], which does not appear to change with improvements in walking distance for PAD patients [23], however there is evidence to suggest that FMD in the leg, rather than the arm, may be a more sensitive measure in this patient group [24,71]. Regardless, the current mix of findings is promising, but indicates a need for further investigation into the therapeutic benefits of dietary NO 3 − supplementation for individuals with cardiovascular disease.…”