Chronic intermittent hypoxia induces oxidative stress and decreases NO production in the carotid artery of rats

Abstract

Obstructive sleep apnea (OSA) syndrome is a risk factor of hypertension and stroke. Chronic intermittent hypoxia (CIH) leads to oxidative stress and tissue injury. We examined the hypothesis that CIH-induced oxidative stress plays a pathophysiological role in the endothelial dysfunction in rat carotid artery. Adult Sprague-Dawley rats were exposed to IH treatment mimicking a severe OSA condition for 14 days. The carotid arteries were harvested for the malondialdehyde assay, PCR and Western-blotting analysis, and the measurement of nitric oxide (NO) with electrochemistry. Levels of malondialdehyde were significantly elevated in the hypoxic group when compared to the normoxic control. Also, the mRNA expressions of NADPH oxidase (gp91phox, p22phox) were markedly increased in the hypoxic group, indicating an involvement in the CIH-induced oxidative stress. In addition, the protein level of phosphorylated eNOS (ser1177) and the NO levels were notably lowered in the hypoxic group. These results suggest that oxidative stress induced by the CIH treatment deteriorates the endothelial function of the carotid artery with decreased NO bioavailability. These data may be clinically relevant to the increased risk for cerebrovascular disease in OSA patients.