PDF(Pubmed)
Abstract：
BACKGROUND: Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension.
RESULTS: Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs.
CONCLUSIONS: Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.
RESULTS: Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs.
CONCLUSIONS: Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.
摘要：
背景：阻塞性睡眠呼吸暂停（OSA）的特征是慢性间歇性缺氧（CIH）的反复发作，这与交感神经兴奋和高血压的发展有关。此外，已经显示CIH在孤束核（NTS）中引起炎症和神经元过度激活，参与交感神经和心血管调节的关键脑干区域。由于一些研究提出NTS星形胶质细胞可能介导神经炎症,我们旨在确定NTS-星形胶质细胞在CIH诱导的高血压发病机制中的潜在作用.
结果：21天的CIH诱发大鼠自主神经失衡和高血压。值得注意的是,使用设计师专用受体（DREADD）恢复的正常心脏变异性（LF/HF：1.1±0.2vs.2.4±0.2vs.1.4±0.3，Shamvs.CIHvs.CIH+CNO,分别）和显着降低暴露于CIH的大鼠的动脉血压（MABP：82.7±1.2vs.104.8±4.4vs.89.6±0.9mmHg，Shamvs.CIHvs.CIH+CNO,分别)。此外,通过使用DREADDs对NTS星形胶质细胞的化学遗传学抑制,也完全消除了暴露于CIH的大鼠急性低氧化学反射激活引起的交感神经兴奋.
结论：我们的结果支持NTS星形胶质细胞在长期暴露于模拟OSA的间歇性缺氧期间维持增强的交感神经驱动和高血压中的作用。
结果：21天的CIH诱发大鼠自主神经失衡和高血压。值得注意的是,使用设计师专用受体（DREADD）恢复的正常心脏变异性（LF/HF：1.1±0.2vs.2.4±0.2vs.1.4±0.3，Shamvs.CIHvs.CIH+CNO,分别）和显着降低暴露于CIH的大鼠的动脉血压（MABP：82.7±1.2vs.104.8±4.4vs.89.6±0.9mmHg，Shamvs.CIHvs.CIH+CNO,分别)。此外,通过使用DREADDs对NTS星形胶质细胞的化学遗传学抑制,也完全消除了暴露于CIH的大鼠急性低氧化学反射激活引起的交感神经兴奋.
结论：我们的结果支持NTS星形胶质细胞在长期暴露于模拟OSA的间歇性缺氧期间维持增强的交感神经驱动和高血压中的作用。
