dimethylarginine and Sleep-Apnea--Obstructive

Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease.. In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed.. Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.

Topics: Adult; Aged; Arginine; Brachial Artery; Continuous Positive Airway Pressure; Endothelium, Vascular; Humans; Male; Middle Aged; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitrites; Sleep Apnea, Obstructive; Vasodilation

Obstructive sleep apnea-hypopnea syndrome (OSAHS) with episodic hypoxia-reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (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 homocysteine 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 > or = 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 production 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.

Topics: Arginine; Body Mass Index; Cardiovascular Diseases; Female; Homocysteine; Humans; Male; Middle Aged; Nitric Oxide; Oxidative Stress; Polysomnography; Severity of Illness Index; Sleep Apnea, Obstructive