Plasma nitrite response and arterial reactivity differentiate vascular health and performance

Abstract

NO is crucial for endothelial function and vascular health. Plasma nitrite (NO(2)(-)) is the main oxidation product of NO and has been shown to reflect changes in eNOS activity. We hypothesized that plasma NO(2)(-) 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 10min following maximal exercise. Plasma samples were analyzed by reductive chemiluminescence. Brachial diameters were imaged prior to, during and following 5min of forearm occlusion (BAFMD). There were no differences in resting plasma NO(2)(-) or BA diameters between groups. The PAD groups had lower age adjusted BAFMD responses (p0.05). Within group analysis revealed an increase in NO(2)(-) 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) (p0.05). DeltaNO(2)(-) and BAFMD were the strongest independent predictors of VO(2peak) in multivariate linear regression. These findings suggest DeltaNO(2)(-) discriminates severity of cardiovascular disease risk, is related to endothelial function and predicts exercise capacity.

Figure 1. Brachial artery flow mediated dilation peak percent changes in diameter from baseline

All values are statically adjusted for differences in age between groups. * = significantly different at the p≤0.05 level.

Figure 2. VO_2peak (ml/kg/min) values during treadmill maximal graded exercise testing

All values are statically adjusted for differences in age between groups *= significantly different at the p≤0.05 level. ** = significantly different at the p<0.01 level

Figure 3. Changes in circulating plasma NO₂- prior to and following a maximal GXT

Samples were collected prior to (pre), and 10 min following (post) GXT. Data is represented as actual NO₂- yield (nM) for each group. Values are statistically adjusted for differences between groups in age and VO_2peak. * = significantly different within groups at the p≤0.05 level. ** = significantly different between groups at the p≤0.01 level.

Figure 4. Changes in circulating plasma NO₃- prior to and following a maximal GXT

Samples were collected prior to (pre), and 10 min following (post) GXT. Data is represented as actual NO₃- yield (uM) for each group. Values are statistically adjusted for differences between groups in age and VO_2peak. * = significantly different between groups at the p≤0.05 level.