Plasma nitrite flux predicts exercise performance in peripheral arterial disease after 3months of exercise training

Plasma nitrite is a major oxidation product of nitric oxide. It has also recently been suggested to perform an endocrine-like function as a nitric oxide donor in hypoxic tissues, allowing vasodilation. Exercise performance is limited in peripheral arterial disease because of an inadequate blood supply to working tissues. We hypothesized that exercise training in peripheral arterial disease subjects will improve "plasma nitrite flux" and endothelial function, to accompany increased exercise performance. Peripheral arterial disease subjects were tested at baseline and after 3months supervised or home exercise training. Venous blood (arm) was drawn at rest and 10min after a maximal graded treadmill test. Samples were added to heparin and centrifuged and plasma was snap-frozen for analysis by reductive chemiluminescence. Brachial artery endothelial function was measured in response to a hyperemic stimulus (flow-mediated dilation). At 3months the peripheral arterial disease-supervised exercise group showed increases in claudication onset pain time (+138s, p≤0.05), peak walking time (+260s, p≤0.01), VO_2peak (1.3ml/kg/min, p≤0.05), brachial artery flow-mediated dilation (+2%, p≤0.05), and plasma nitrite flux (+33% p≤0.05). There were no changes in the peripheral arterial disease-home exercise group. The change in plasma nitrite flux predicted the change in claudication onset pain (r²=0.59, p≤0.01). These findings suggest that changes in plasma nitrite are related to endothelial function and predict exercise performance in peripheral arterial disease.