Low but not high frequency of intermittent hypoxia suppresses endothelium-dependent, oxidative stress-mediated contractions in carotid arteries of obese mice

• Published in: Journal of applied physiology (1985) 2018-11, Vol.125 (5), p.1384-1395
• Main Authors: Lee, Mary Y K, Ge, Grace, Fung, M L, Vanhoutte, Paul M, Mak, Judith C W, Ip, Mary S M
• Format: Article
• Language: English
• Subjects: Acetylcholine; Antioxidants; Apnea; Arteries; Blood pressure; Carotid arteries; Carotid artery; Diet; Endothelium; Exposure; High fat diet; Hypoxia; Isometric; Malondialdehyde; Mice; NG-Nitroarginine methyl ester; Nitric oxide; Nitric-oxide synthase; Obesity; Oxidative stress; Preconditioning; Risk analysis; Risk factors; Rodents; Serum levels; Sleep; Sleep disorders
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00224.2018

Obstructive sleep apnea is characterized by intermittent hypoxia (IH) during sleep and predisposes to endothelial dysfunction. Obesity is a major risk factor for the occurrence of sleep apnea. The present study compared the functional impact of low- (IH10; 10 hypoxic events/h) and high-frequency (IH60; 60 hypoxic events/h) IH for 4 wk on endothelial function in male C57BL/6 mice with or without high-fat (HF) diet-induced obesity. Mean arterial blood pressure (tail cuff method) was increased in obese mice after IH60 exposure, i.e., HF + IH60 group. The serum levels of the oxidative stress marker malondialdehyde were augmented in lean IH60 and HF groups, with a further increase in HF + IH60 but a reduction in HF + IH10 mice compared with the HF group. Vascular responsiveness was assessed as changes in isometric tension in isolated arteries. Relaxations to the endothelium-dependent vasodilator acetylcholine were impaired in HF + IH60 aortae. Endothelium-dependent contractions (EDC; response to acetylcholine in the presence of the nitric oxide synthase inhibitor l-NAME) in carotid arteries were augmented in the HF group, but this HF-induced augmentation was suppressed by low-frequency IH exposure. The addition of apocynin (antioxidant) reduced EDC in HF and HF + IH60 groups but not in HF + IH10 group. In conclusion, these findings suggest that exposure of obese mice to mild IH exerts preconditioning-like suppression of endothelium-dependent and oxidative stress-mediated contractions. When IH severity increases, this suppression diminishes and endothelial dysfunction accelerates. NEW & NOTEWORTHY The present study demonstrates, for the first time, that low-frequency intermittent hypoxia may exert a preconditioning-like suppression of oxidative stress-induced endothelium-dependent contractions in mice with diet-induced obesity. This relative suppression was diminished as intermittent hypoxia became more severe, and a deleterious effect on endothelial function emerged.