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

Abstract

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 due to an inadequate blood supply to working tissues. We hypothesized that exercise training in peripheral arterial disease subjects will demonstrate improved "plasma nitrite flux" and endothelial function, to accompany increased exercise performance. Peripheral arterial disease subjects were tested at baseline and following 3 months supervised or home exercise training.Venous blood (arm) was drawn at rest and 10min following a maximal graded treadmill test. Samples were added to heparin, centrifuged and plasma snap frozen for analysis by reductive chemiluminescence. Brachial artery endothelial function was measured in response to a hyperemic stimulus (flow-mediated dilation). At 3 months the peripheral arterial disease-supervised exercise group showed increases in claudication onset pain time (+138sec, p≤0.05) peak walking time (+260sec, 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 changes in plasma nitrite are related to endothelial function and predict exercise performance in peripheral arterial disease.

Sodium nitrite in patients with peripheral artery disease and diabetes mellitus: Safety, walking distance and endothelial function

“…11 Nitrite stores decrease following exercise among individuals with PAD, with and without diabetes (40% reduction), compared with healthy individuals. 12,13 These results are consistent with use of NO stores in an attempt to normalize blood flow and oxygen delivery. As nitrite stores become depleted, the resulting loss of NO may contribute to abnormal endothelial function and circulatory responses in PAD.…”

The impact of different supervised exercise regimens on endothelial function in patients with intermittent claudication

“…23 Failure to control for the impact of diet on NO levels is not only a limitation of our study but also of previous studies which in contrast to us, have demonstrated improvement in NO bioavailability following SET in claudicants. 24 A variation in dietary intake may therefore provide some explanation for such contrasting results. Furthermore, Allen et al 24 measured nitrite levels only which are rapidly metabolised to nitrate and therefore unlikely to provide an accurate representation of total endogenous NO production.…”

Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease

“…It is well established that NO availability declines with age [11,12] and can be further compromised by the presence of atherosclerotic disease, as observed in PAD [13]. However, the cause for low NO availability in PAD is unknown.…”

“…In PAD, there is evidence that NO availability is closely associated with exercise tolerance [13]. We assessed the relationship between leg blood flow and amounts of the enzymes that produce NO and ROS, as ROS production directly impacts NO bioavailability [17].…”