Effects Of Dietary Nitrate On Skeletal Muscle Microvascular And Autonomic Function In Peripheral Artery Disease

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by compromised lower-extremity blood flow that impairs walking capacity. We recently showed that a moderate body mass-normalized dose of dietary nitrate in the form of beetroot juice (BRJ, 0.11 mmol/kg) can improve macrovascular function and maximal walking distance in patients with PAD. However, its impacts on the skeletal muscle microcirculation and autonomic nervous system have not been investigated. PURPOSE: To investigate the effects of a moderate dose of dietary nitrate on skeletal muscle microvascular function and autonomic nervous system function and to further relate these measurements to walking distance and symptom onset in patients with PAD. METHODS: Patients with PAD (n = 10) ingested either BRJ or placebo in a randomized crossover design. Autonomic nervous system function, skeletal muscle microvascular function, and 6-min walking distance were assessed by heart rate variability, reactive hyperemia with near-infrared spectroscopy (tissue oxygenation index (TOI) recovery rate), and the 6-min walk test, respectively, pre- and post-BRJ and placebo intake. RESULTS: There were significant group x time interactions (P < 0.05) for skeletal muscle microvascular function and 6-min walking distance whereas no changes (P > 0.05) occurred in heart rate variability or pain-free walking distance. The BRJ group demonstrated improved skeletal muscle microvascular function (Δ 22.1 ± 7.5%·min-1) and a longer 6-min walking distance (Δ 37.5 ± 9.1 m). Furthermore, TOI recovery rate was positively associated with 6-min walking distance (r = 0.5) and pain-free walking distance (r = 0.6). CONCLUSIONS: These results suggest that a moderate dose of dietary nitrate may support skeletal muscle microvascular function, which is related to improvements in 6-min and pain-free walking distance in patients with PAD. Supported by the NIH [R01 HD106911-01A1 and R01 AG077803] and Center for Research in Human Movement Variability [P20GM109090], the University of Nebraska (UNO) Collaboration Initiative Grant [32105], the UNO Graduate Research and Creative Activity grant, the NASA Nebraska Space Grant Fellowship, and the NASA Nebraska Space Grant [NNX15AI09H and 80NSSC20M0112]. No relationships reported.