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 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 3 months supervised or home exercise training. Venous blood (arm) was drawn at rest and 10 min 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 3 months the peripheral arterial disease-supervised exercise group showed increases in claudication onset pain time (+138 s, p< or =0.05), peak walking time (+260 s, p< or =0.01), VO(2peak) (1.3 ml/kg/min, p< or =0.05), brachial artery flow-mediated dilation (+2%, p< or =0.05), and plasma nitrite flux (+33% p< or =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 (r(2)=0.59, p< or =0.01). These findings suggest that changes in plasma nitrite are related to endothelial function and predict exercise performance in peripheral arterial disease.

Figure 1

A–C:- Exercise Performance Measures at Baseline and following 3 months of Supervised or Home Exercise. Changes in (A) Time to Claudication Onset Pain (sec), (B) Peak Walking Time (sec), and (C) VO_2peak (ml/kg/min) from baseline (BASE) to 3 months post (3M) supervised exercise training (SE) or instructions to exercise at home (HE). Values are mean±SE. * = p≤0.05, ** =. p≤0.01. PAD = peripheral arterial disease subjects, CON = Controls

Figure 2

Brachial Artery Flow-Mediated Dilation at Baseline (BASE) and following 3 months (3M) of supervised (SE) or home exercise (HE). Values are mean±SE. * = p≤0.05. PAD = peripheral arterial disease subjects, CON = Controls

Figure 3

A–B:- Plasma Nitrite prior to and following a maximal Cardiopulmonary Exercise Testing (CPX). Changes in (A) Circulating plasma nitrite concentration (nM) and (B) plasma nitrite flux (%change in plasma nitrite concentration for pre to post CPX) for both baseline (0M) and 3 month (3M) visits. Samples were collected prior to (Rest), and 10 min following CPX (CPX). * = significantly different within groups at the p≤0.05 level. ** = significantly different within groups at the p≤0.01 level. δ = significantly different between groups at the p≤0.05 level. PAD = peripheral arterial disease subjects, CON = Controls, SE = supervised exercise training, HE = instructed to exercise at home

Figure 4

Relationship between the Change in Time to Claudication Onset Pain (COT) and Change in Plasma Nitrite Flux in Peripheral Arterial Disease subjects following 3 months of study intervention.