Nitric oxide (NO) bioavailability is important in vascular health, but unsuitable as a clinical measure due to biological oxidation. Total nitrogen oxides (NO,) are stable but background nitrate levels make it difficult to detect disease-based variation. We investigated the clinical discriminatory value of NO, as it relates to exercise capability (VO2peak) 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 degrees C, filtered, and stored at -70 degrees C. NOx 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 VO2peak, HDL levels, and baseline NOx values than the RF (n 15) and CVD (n = 10) groups. NOx increased from baseline to recovery in the H group only (75.85 +/- 19.04 mu M vs 97.76 +/- 31.93 mu M; 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 VO2peak and NOx recovery was significant across groups (r = 0.71, P <= 0.01). Following training the RF subjects (n = 7) increased VO2peak (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 NOx (18.29 +/- 6.46 to 66.48 +/- 21.11 mu M; P <= 0.01). These findings suggest that plasma NOx following GXT discriminate cardiovascular disease status, are related to regional endothelial function, and respond favorably to exercise training. (c) 2006 Elsevier Inc. All rights reserved.