Chen Jin, Gu He, Wurster Robert D, Cheng Zixi Jack
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida.
Department of Cellular and Molecular Physiology, Stritch School of Medicine, Loyola University, Maywood, Illinois.
Am J Physiol Regul Integr Comp Physiol. 2021 Mar 1;320(3):R317-R330. doi: 10.1152/ajpregu.00147.2020. Epub 2020 Dec 9.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.
阻塞性睡眠呼吸暂停（OSA）是一种高度流行的睡眠障碍，与许多心血管并发症相关。与OSA相似，慢性间歇性缺氧（CIH）（一种OSA模型）会导致氧化应激，并损害啮齿动物心率（HR）的压力反射控制。压力反射弧包括主动脉减压神经（ADN）、迷走神经传出纤维和中枢神经元。在本研究中，我们以小鼠为模型，研究CIH对压力反射敏感性、主动脉压力感受器传入纤维以及压力反射通路的中枢和迷走神经传出成分的影响。此外，我们测试了转基因小鼠中人类铜/锌超氧化物歧化酶（SOD1）的过表达是否能保护其免受CIH诱导的压力反射弧缺陷的影响。将野生型C57BL/6J小鼠和SOD1小鼠暴露于常氧（RA）或CIH环境中，然后进行麻醉、通气并插入导管，以测量平均动脉压（MAP）和HR。与野生型RA对照组相比，CIH损害了压力反射敏感性，但增加了最大压力感受器增益和对迷走神经传出刺激的心动过缓反应。此外，CIH降低了对ADN刺激的心动过缓反应，表明心动过缓的中枢调节减弱。有趣的是，SOD1的过表达可防止CIH诱导的转基因小鼠对ADN刺激的HR反应减弱，并保留对迷走神经传出刺激的HR反应。我们认为，CIH降低了压力反射的中枢调节作用，而SOD1的过表达可能预防CIH诱导的中枢缺陷。
