ORIGINAL ARTICLE Circulating nitric oxide (NO), asymmetric dimethylarginine (ADMA), homocysteine, and oxidative status in obstructive sleep apnea–hypopnea syndrome (OSAHS) Yeşim Ozkan & Hikmet Fırat & Bolkan Şimşek & Meral Torun & Sevgi Yardim-Akaydin Published online: 6 October 2007 # Springer-Verlag 2007 Abstract Obstructive sleep apnea–hypopnea syndrome (OSAHS) with episodic hypoxia–reoxygenation is associ- ated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethy- larginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homo- cysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO 2 (r =0.513, p <0.002) and lowest SaO 2 (r =0.363, p <0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI=5–29) and severe (AHI ≥ 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p <0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = -0.415, p <0.02) and also in severe OSAHS group (r = -0.641, p < 0.007). Hyperhomocysteinemia and diminished NO pro- duction may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS. Keywords ADMA . Apnea . Homocysteine . Nitric oxide . Oxidative status . Sleep apnea Introduction Obstructive sleep apnea–hypopnea syndrome (OSAHS) is characterized by repetitive apnea and hypopnea attacks followed by arousals and affects patients’ physical, emo- tional, and intellectual capacities and functional quality of life. OSAHS has been linked to increased prevalence of cardiovascular and cerebrovascular diseases, stroke, meta- bolic syndrome, cognitive impairment, and systemic or pulmonary hypertension [1, 2]. Therefore, recent research has focused on exact mechanisms for the elucidation of the relationships between these diseases and OSAHS. Changes in ventilatory function and concomitant sleep disruption may result in a cascade of events including oxidative stress, inflammation, vascular endothelial dys- function, and metabolic dysregulation. Repeated apnea- related hypoxic events in OSAHS are similar to hypoxia/ Sleep Breath (2008) 12:149–154 DOI 10.1007/s11325-007-0148-4 Y. Ozkan (*) : B. Şimşek : M. Torun : S. Yardim-Akaydin Department of Biochemistry, Faculty of Pharmacy, Gazi University, 06330 Etiler, Ankara, Turkey e-mail: yesim@gazi.edu.tr H. Fırat Sleep Disorders Center, Department of Chest Diseases, Dışkapı Education and Research Hospital, Ankara, Turkey