Effect of Obstructive Sleep Apnea and CPAP Treatment on the Bioavailability of Erythrocyte and Plasma Nitric Oxide

Introduction: Endothelial dysfunction resulting from decreased nitric oxide (NO) bioavailability is an important mechanism that increases cardiovascular risk in subjects with obstructive sleep apnea (OSA). NO is produced by nitric oxide synthase (NOS) in a reaction that converts L-arginine to L-citrulline. Asymmetric-dimethylarginine (ADMA) is created by L-arginine and is a naturally occurring competitive inhibitor of nitric oxide synthase (NOS). The aim of our study was to verify if erythrocytes could play a role in the storage and accumulation of ADMA in OSA patients. The crosstalk between erythrocyte-ADMA, SDMA, L-arginine, and L-citrulline levels and endothelial function was investigated in OSA subjects both at baseline and prospectively following 1-year CPAP (continuous positive airway pressure) treatment. Material and Methods: A total of 46 subjects with OSA were enrolled in this study and divided into two groups: those with moderate-to-severe OSA and those with mild or no OSA. A physical examination was followed by blood collection for the assessment of biochemical cardiovascular risk factors and the nitric oxide bioavailability parameters both in plasma and erythrocytes. Vasodilative endothelial function was assessed using Laser Doppler Flowmetry (LDF). Results: No significant changes regarding the NO pathway metabolites were noted apart from the plasma L-citrulline concentration, which was decreased in patients with OSA (26.9 ± 7.4 vs. 33.1 ± 9.4 μM, p < 0.05). The erythrocyte ADMA concentration was lower than in plasma irrespective of the presence of OSA (0.33 ± 0.12 vs. 0.45 ± 0.08 μM in OSA, p < 0.05 and 0.33 ± 0.1 vs. 0.45 ± 0.07 μM in the control, p < 0.05). No significant changes regarding the LDF were found. CPAP treatment did not change the levels of NO metabolites in the erythrocytes. Conclusions: The erythrocyte pool of the NO metabolic pathway intermediates does not depend on OSA and its treatment, whereas the erythrocytes could constitute a high-volume buffer in their storage Hence, the results from this prospective study are a step forward in understanding the role of the erythrocyte compartment and the intra-erythrocyte pathways regulating NO bioavailability and paracrine endothelial function in the hypoxia-reoxygenation setting, such as obstructive sleep apnea.