Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release

Frontiers in Physiology

Xiaoyu Su²  Ying-Jie Peng²  Nanduri Prabhakar²  Jayasri Nanduri²  Robert B. Hamanaka²  Gökhan M. Mutlu²  Yun Fang²  Parker S. Woods⁴  David Wu⁴  Angelo Y. Meliton⁴  Kaitlyn A. Sun⁴  Rengul Cetin-Atalay⁴ 

[1] Department of Medicine, University of Chicago, Chicago, IL, United States;Institute for Integrative Physiology, University of Chicago, Chicago, IL, United States;Section of Emergency Medicine, University of Chicago, Chicago, IL, United States;Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, United States;

关键词: obstructive sleep apnea;    endothelial cell;    epinephrine (adrenaline);    intermittent hypoxia;    inflammation;   

DOI  :  10.3389/fphys.2021.701995

来源: DOAJ

【 摘 要 】

Obstructive sleep apnea (OSA) is a common breathing disorder affecting a significant percentage of the adult population. OSA is an independent risk factor for cardiovascular disease (CVD); however, the underlying mechanisms are not completely understood. Since the severity of hypoxia correlates with some of the cardiovascular effects, intermittent hypoxia (IH) is thought to be one of the mechanisms by which OSA may cause CVD. Here, we investigated the effect of IH on endothelial cell (EC) activation, characterized by the expression of inflammatory genes, that is known to play an important role in the pathogenesis of CVD. Exposure of C57BL/6 mice to IH led to aortic EC activation, while in vitro exposure of ECs to IH failed to do so, suggesting that IH does not induce EC activation directly, but indirectly. One of the consequences of IH is activation of the sympathetic nervous system and catecholamine release. We found that exposure of mice to IH caused elevation of circulating levels of catecholamines. Inhibition of the IH-induced increase in catecholamines by pharmacologic inhibition or by adrenalectomy or carotid body ablation prevented the IH-induced EC activation in mice. Supporting a key role for catecholamines, epinephrine alone was sufficient to cause EC activation in vivo and in vitro. Together, these results suggested that IH does not directly induce EC activation, but does so indirectly via release of catecholamines. These results suggest that targeting IH-induced sympathetic nerve activity and catecholamine release may be a potential therapeutic target to attenuate the CV effects of OSA.

【 授权许可】

Unknown