Total nitrogen oxide following exercise testing reflects endothelial function and discriminates health status

Nitric oxide (NO) bioavailability is important in vascular health, but unsuitable as a clinical measure due to biological oxidation. Total nitrogen oxides (NO_x) are stable but background nitrate levels make it difficult to detect disease-based variation. We investigated the clinical discriminatory value of NO_x as it relates to exercise capability (VO_2peak) and brachial artery reactivity (BAR, an NO-dependent measure of endothelial health), in healthy (H), increased risk (RF), and known cardiovascular disease (CVD) subjects. BAR was measured using forearm occlusion/hyperemia stimulus. Subjects performed a maximal graded exercise test (GXT). Blood at rest, exercise termination, and 10 min into recovery was mixed equally with 0.1 M NaOH at 4°C, filtered, and stored at -70°C. NO_x was measured by chemiluminescence. Seven of the RF group then exercise-trained for 6 months prior to retesting. The H group (n = 12) was younger, had higher VO_2peak, HDL levels, and baseline NO_x values than the RF (n = 15) and CVD (n = 10) groups. NO_x increased from baseline to recovery in the H group only (75.85 ± 19.04 μM vs 97.76 ± 31.93 μM; P ≤ 0.01). BAR was greater in the H versus CVD group (7.24 ± 3.78% vs 2.59 ± 3.53%; P ≤ 0.01). The relation between VO_2peak and NO_x recovery was significant across groups (r = 0.71, P ≤ 0.01). Following training the RF subjects (n = 7) increased VO_2peak (29.98 ± 6.74 to 33.08 ± 5.57 ml kg^-1 min^-1; P ≤ 0.05), BAR (3.19 ± 3.96 to 6.86 ± 4.81%; P ≤ 0.05), and recovery NO_x (18.29 ± 6.46 to 66.48 + 21.11 μM; P ≤ 0.01). These findings suggest that plasma NO_x following GXT discriminate cardiovascular disease status, are related to regional endothelial function, and respond favorably to exercise training.