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

Abstract

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/hour) and high (IH60; 60 hypoxic events/hour) frequency IH during four weeks 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 to 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.

Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development

“…Scale bar: 50 μm a 3-day infusion of candesartan reduces SAP to the levels found in normotensive rats. The involvement of oxidative stress and inflammatory mediators in the systemic vascular Ang II effects was examined by evaluating the AP changes in response to apocynin administration since it has antioxidative and anti-inflammatory effects [15]. The increment in oxidative stress was confirmed by the sex-dependent elevation of NADPHp67phox expression in the renal cortex and renal medulla of rats with ARDev + HFD.…”

Intermittent hypoxia-related alterations in vascular structure and function: a systematic review and meta-analysis of rodent data

“…Many studies using animal models have supported the hypothesis that IH might be responsible for increased arterial blood pressure 5,6 , structural vascular remodelling [7][8][9] , altered vascular reactivity 10,11 , and atherosclerosis progression [12][13][14] . However, some studies showed no effect of IH on vascular parameters (for example [15][16][17][18] ) and there was heterogeneity regarding effect size.…”

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

“…Interesting outcomes were shown in a mice model study, where the animals treated with a high-fat diet revealed a positive effect of the low-frequency hypoxia. The serum levels of the oxidative stress markers were increased in the mice treated with a high-frequency intermittent hypoxia (60 hypoxic events/h) and decreased by treating with a low frequency hypoxia (10 events/h) [ 41 ]. That could be partially explained by the activation of protective mechanisms during IH.…”