ndothelial dysfunction is recognized as an early phase of arteriosclerosis 1 and an important cause of that dysfunction is impaired nitric oxide (NO) release from the endothelium. Endothelial NO is a key regulator of vascular homeostasis; it induces vasorelaxation by generating cyclic GMP in the underlying smooth muscle cells, and prevents monocyte adhesion to the endothelium, platelet activation, and smooth muscle cell proliferation. Hence, impaired NO release from injured endothelial cells is regarded as an initiator and promoter of arteriosclerosis.Endothelial NO is produced when L-arginine is con- February 2005 verted to L-citrulline by the enzyme endothelial nitric oxide synthase (eNOS). Endothelial NOS is inhibited by endogenous inhibitors, NG-monomethyl-L-arginine (L-NMMA) and asymmetric dimethylarginine (ADMA), which are structural analogues of L-arginine. 2,3 Plasma ADMA is eliminated by renal excretion and by degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). 4 Increased plasma concentration of ADMA is associated with hypertension, 5 pulmonary hypertension, 6 hypercholesterolemia, 7,8 carotid intima -media thickening, 9 severe peripheral artery occlusive disease, 10 and the clustering of coronary risk factors. 9 These findings suggest that ADMA is responsible for endothelial dysfunction. Obstructive sleep apnea syndrome (OSAS) has been recently attracting attention as a significant disorder. Frequent apnea/hypopnea attacks followed by arousal results in insufficient sleep at night, causing daytime sleepiness, leading to work inefficiency, and even traffic accidents. In addition, OSAS often accompanies hypertension, obesity, glucose intolerance, and dyslipidemia, all of which are factors in metabolic syndrome. Hence, OSAS is recognized as a risk factor for cardiovascular disease. 11-14 It has been Background 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.
Methods and ResultsIn 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, bu...
