Obstructive sleep apnea (OSA) has been increasingly linked to cardiovascular disease, endothelial dysfunction, and oxidative stress, generated by repetitive nocturnal hypoxemia and reperfusion. Circulating free nitrotyrosine has been reported as a novel biomarker of nitric oxide (NO)-induced oxidative/nitrosative stress. Nitrosative stress has been implicated as a possible mechanism for development of cardiovascular diseases. We tested the hypothesis that repetitive severe hypoxemia resulting from OSA would increase NO-mediated oxidative stress. We studied 10 men with newly diagnosed moderate to severe OSA who were free of other diseases, had never been treated for OSA, and were taking no medications. Nitrotyrosine measurements, performed by liquid chromatography-tandem mass spectrometry, were made before and after untreated apneic sleep. We compared free nitrotyrosine levels in these patients with those obtained at similar times in 10 healthy male control subjects without OSA, with similar age and body mass index. Evening baseline nitrotyrosine levels were similar before sleep in the control and OSA groups [0.16 Ϯ 0.01 and 0.15 Ϯ 0.01 ng/ml, respectively, P ϭ not significant (NS)]. Neither normal nor disturbed apneic sleep led to significant changes of plasma nitrotyrosine (morning levels: control group 0.14 Ϯ 0.01 ng/ml; OSA group 0.15 Ϯ 0.01 ng/ml, P ϭ NS). OSA was not accompanied by increased circulating free nitrotyrosine either at baseline or after sleep. This observation suggests that repetitive hypoxemia during OSA does not result in increased NO-mediated oxidative/nitrosative stress in otherwise healthy subjects with OSA. nitric oxide; cardiovascular diseases OBSTRUCTIVE SLEEP APNEA (OSA) has been linked to increased prevalence of cardiovascular and cerebrovascular morbidity (43). OSA is characterized by repetitive episodes of apnea and hypopnea that lead to surges in arterial blood pressure and increased sympathetic nerve activity (37, 45). More recently, OSA has also been associated with inflammation (35, 39, 44), endothelial dysfunction (19, 22) and increased oxidative stress (6,9,23,32), generated by repetitive nocturnal hypoxemia and reoxygenation. However, the mechanisms for increased cardiovascular disease in OSA are not fully understood.Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the most important free radicals in the human body causing increased oxidative/nitrosative stress and tissue injury under pathological conditions (20, 31). Emerging evidence suggests that ROS are involved in the development and progression of a wide range of cardiovascular diseases (1,14,27,30). Recent studies also indicate that RNS may likewise contribute to cardiovascular disease, including vascular inflammation, endothelial dysfunction, coronary artherosclerosis, hypertension, and heart failure (2,3,7,15,36,41). OSA has been strongly linked to oxidative stress (6, 9, 23, 32); however, the effects of OSA on RNS have not been evaluated.Peroxynitrite (ONNO Ϫ ) and other RNS are generated by t...