Plasma nitrite response and arterial reactivity differentiate vascular health and performance

NO is crucial for endothelial function and vascular health. Plasma nitrite (NO₂^-) is the main oxidation product of NO and has been shown to reflect changes in eNOS activity. We hypothesized that plasma NO₂^- response to physical exercise stress along with physiological endothelial function would be reduced with increasing severity of vascular disease. Subject groups were: (a) risk factors but no vascular disease (RF); (b) Type 2 diabetes with no vascular disease (DM); (c) diagnosed peripheral arterial disease (PAD); and (d) DM + PAD. Venous blood was drawn at rest and 10 min following maximal exercise. Plasma samples were analyzed by reductive chemiluminescence. Brachial diameters were imaged prior to, during and following 5 min of forearm occlusion (BAFMD). There were no differences in resting plasma NO₂^- or BA diameters between groups. The PAD groups had lower age adjusted BAFMD responses (p ≤ 0.05). Within group analysis revealed an increase in NO₂^- in the RF group (+39.3%), no change in the DM (-15.51%), and a decrease in the PAD (-44.20%) and PAD + DM (-39.95%). This was maintained after adjusting for age and VO_2peak (p ≤ 0.05). ΔNO₂^- and BAFMD were the strongest independent predictors of VO_2peak in multivariate linear regression. These findings suggest ΔNO₂^- discriminates severity of cardiovascular disease risk, is related to endothelial function and predicts exercise capacity.