Moderate dose of dietary nitrate improves skeletal muscle microvascular function in patients with peripheral artery disease.

Peripheral artery disease (PAD) is an atherosclerotic disease characterized by compromised lower-extremity blood flow that impairs walking ability. We showed that a moderate 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 microcirculation and autonomic nervous system have not been examined. Therefore, we investigated the impacts of this dose of dietary nitrate on skeletal muscle microvascular function and autonomic nervous system function and further related these measurements to 6-min walking distance, pain-free walking distance, and exercise recovery in patients with PAD. Patients with PAD (n = 10) ingested either BRJ or placebo in a randomized crossover design. Heart rate variability, skeletal muscle microvascular function, and 6-min walking distance were performed pre- and post-BRJ and placebo. There were significant group × time interactions (P < 0.05) for skeletal muscle microvascular function, 6-min walking distance, and exercise recovery, but no changes (P > 0.05) in heart rate variability or pain-free walking distance were noted. The BRJ group demonstrated improved skeletal muscle microvascular function (∆ 22.1 ± 7.5 %·min-1), longer 6-min walking distance (Δ 37.5 ± 9.1 m), and faster recovery post-exercise (Δ -15.3 ± 4.2 s). Furthermore, changes in skeletal muscle microvascular function were positively associated with changes in 6-min walking distance (r = 0.5) and pain-free walking distance (r = 0.6). These results suggest that a moderate dose of dietary nitrate may support microvascular function, which is related to improvements in walking distance and claudication in patients with PAD.

Microvascular Dysfunction in Peripheral Artery Disease: Is Heat Therapy a Viable Treatment?

Peripheral artery disease (PAD) is characterized by the development of atherosclerotic plaques in the lower-body conduit arteries. PAD is commonly accompanied by microvascular disease, which may result in poor wound healing, plantar ulcer development, and subsequent limb amputation. Understanding the mechanisms underlying the development of plantar ulcers is a critical step in the development of adequate treatment options for patients with PAD. Skin is classified into two major components: glabrous and non-glabrous. These skin types have unique microcirculation characteristics, making it important to differentiate between the two when investigating mechanisms for plantar ulcer development in PAD. There is evidence for a microcirculation compensatory mechanism in PAD. This is evident by the maintenance of basal microcirculation perfusion and capillary filling pressure despite a reduced pressure differential beyond an occlusion in non-critical limb ischemia PAD. The major mechanism for this compensatory system seems to be progressive vasodilation of the arterial network below an occlusion. Recently, heat therapies have emerged as novel treatment options for attenuating the progression of PAD. Heat therapies are capable of stimulating the cardiovascular system, which may lead to beneficial adaptations that may ultimately reduce fatigue during walking in PAD. Early work in this area has shown that full-body heating is capable of generating an acute cardiovascular response, similar to exercise, which has been suggested as the most efficient treatment modality and may generate adaptations with chronic exposure. Heat therapies may emerge as a conservative treatment option capable of attenuating the progression of PAD and ultimately impeding the development of plantar ulcers.