Laboratory of Cardiorespiratory Control, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Instituto de Fisiología, Universidad Austral de Chile, Valdivia, Chile.
Biol Res. 2023 Nov 6;56(1):57. doi: 10.1186/s40659-023-00463-0.
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.
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.
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.
阻塞性睡眠呼吸暂停（OSA）的特征是反复发作的慢性间歇性低氧（CIH），这与交感兴奋和高血压的发展有关。此外，已经表明，CIH 诱导孤束核（NTS）中的炎症和神经元过度兴奋，NTS 是参与交感和心血管调节的关键脑干区域。由于几项研究提出 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。
21 天的 CIH 导致大鼠自主神经失衡和高血压。值得注意的是，使用 Designer Receptors Exclusively Activated by Designers Drugs（DREADD）对延髓 NTS 星形胶质细胞进行急性化学遗传抑制（CNO），可恢复正常的心脏变异性（LF/HF：1.1±0.2 对 2.4±0.2 对 1.4±0.3，Sham 对 CIH 对 CIH+CNO，分别），并显著降低暴露于 CIH 的大鼠的动脉血压（MABP：82.7±1.2 对 104.8±4.4 对 89.6±0.9mmHg，Sham 对 CIH 对 CIH+CNO，分别）。此外，使用 DREADD 对 NTS 星形胶质细胞进行化学遗传抑制，完全消除了急性低氧化学感受器激活在 CIH 暴露大鼠中引发的交感神经兴奋增强。
我们的结果支持 NTS 星形胶质细胞在模拟 OSA 的慢性间歇性低氧暴露期间维持升高的交感神经驱动和高血压中的作用。
