Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats
Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats
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DOI：
10.1161/hypertensionaha.116.07255
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发表时间：
2016-08-01
期刊：
影响因子：
8.3
通讯作者：
Iturriaga, Rodrigo
中科院分区：
文献类型：
--
作者：
Del Rio, Rodrigo;Andrade, David C.;Iturriaga, Rodrigo
慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停的主要特征，可增强颈动脉体（CB）对缺氧的化学感受性反应，并产生自主神经功能障碍、心律失常和高血压。我们通过消融CB化学感受器，检测了CIH诱导的自主神经改变、血管生成和高血压进展是否依赖于CB化学感受驱动的增强。雄性Sprague-Dawley大鼠暴露于对照（Sham）条件7天，然后暴露于CIH（5%O-2，12/h 8 h/d）共28天。在CIH暴露21天时，大鼠接受双侧CB消融，然后再暴露于CIH 7天。在清醒大鼠上测定动脉血压和低氧诱导的化学感受性反射。此外，在实验期间评估心脏自主神经失衡、心脏压力反射增益和心律失常评分。在单独的实验系列中，我们测量了心脏心房组织和全身氧化应激中的细胞外基质重塑含量。CIH诱导高血压，增强对缺氧的反应，诱导交感神经优势的自主神经失衡，减少压力反射增益，增加心律失常和心房纤维化。CB消融使血压正常化，减少对缺氧的反应，并恢复心脏自主神经和压力反射功能。此外，CB消融减少了心律失常的数量，但没有细胞外基质重塑或全身氧化应激，表明CIH期间心律失常发生率的降低与心脏自主平衡的正常化有关。目前的研究结果表明，CIH引起的自主神经功能的改变是严重依赖于CB和CB在CIH引起的高血压支持的主要作用。
Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O-2, 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments. In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and increased arrhythmias and atrial fibrosis. CB ablation normalized blood pressure, reduced ventilatory response to hypoxia, and restored cardiac autonomic and baroreflex function. In addition, CB ablation reduced the number of arrhythmias, but not extracellular matrix remodeling or systemic oxidative stress, suggesting that reductions in arrhythmia incidence during CIH were related to normalization of cardiac autonomic balance. Present results show that autonomic alterations induced by CIH are critically dependent on the CB and support a main role for the CB in the CIH-induced hypertension.