Abstract：
OBJECTIVE: Activation of central respiratory chemoreceptors provides excitatory drive to both respiratory and sympathetic outputs. The enhanced respiratory-sympathetic coupling contributes to the onset and development of hypertension. However, the specific central targets and molecular mechanisms involved in this process remain elusive. This study aimed to investigate the role of acid-sensing ion channel 1 (ASIC1) in nucleus tractus solitarii (NTS) neurons in CO2-stimulated cardiorespiratory effects in spontaneously hypertensive rats (SHRs).
METHODS: Respiration and blood pressure of conscious rats were recorded by whole-body plethysmography and telemetry, respectively. Western blot was used to detect the expression difference of ASIC1 protein in NTS region between Wistar-Kyoto (WKY) rats and SHRs. Excitability of NTS neurons were assessed by extracellular recordings.
RESULTS: Compared to WKY rats, the enhanced CO2-stimulated cardiopulmonary effect and up-regulation of ASIC1 in the NTS were already observed in 4-week-old prehypertensive SHRs. Furthermore, specific blockade of ASIC1 effectively attenuated the CO2-stimulated increase in firing rate of NTS neurons in anesthetized adult SHRs. Intracerebroventricular injections of the ASIC1a blocker PcTx1 or knockdown Asic1 in NTS neurons significantly reduced the heightened CO2-stimulated ventilatory response, and diminished the CO2-stimulated increase in arterial pressure and heart rate in adult SHRs.
CONCLUSIONS: These findings showed that dysregulated ASIC1 signaling in the NTS contribute to the exaggerated CO2-stimulated cardiorespiratory effects observed in SHRs.
METHODS: Respiration and blood pressure of conscious rats were recorded by whole-body plethysmography and telemetry, respectively. Western blot was used to detect the expression difference of ASIC1 protein in NTS region between Wistar-Kyoto (WKY) rats and SHRs. Excitability of NTS neurons were assessed by extracellular recordings.
RESULTS: Compared to WKY rats, the enhanced CO2-stimulated cardiopulmonary effect and up-regulation of ASIC1 in the NTS were already observed in 4-week-old prehypertensive SHRs. Furthermore, specific blockade of ASIC1 effectively attenuated the CO2-stimulated increase in firing rate of NTS neurons in anesthetized adult SHRs. Intracerebroventricular injections of the ASIC1a blocker PcTx1 or knockdown Asic1 in NTS neurons significantly reduced the heightened CO2-stimulated ventilatory response, and diminished the CO2-stimulated increase in arterial pressure and heart rate in adult SHRs.
CONCLUSIONS: These findings showed that dysregulated ASIC1 signaling in the NTS contribute to the exaggerated CO2-stimulated cardiorespiratory effects observed in SHRs.
摘要：
目的：中枢呼吸化学感受器的激活为呼吸和交感神经输出提供了兴奋驱动。增强的呼吸-交感神经耦合有助于高血压的发生和发展。然而,参与这一过程的特定中心靶标和分子机制仍然难以捉摸。本研究旨在探讨酸敏感离子通道1（ASIC1）在自发性高血压大鼠（SHR）CO2刺激的心肺效应中的作用。
方法：通过全身体积描记术和遥测记录清醒大鼠的呼吸和血压，分别。Westernblot检测Wistar-Kyoto（WKY）大鼠和SHRNTS区ASIC1蛋白表达差异。通过细胞外记录评估NTS神经元的兴奋性。
结果：与WKY大鼠相比，在4周龄高血压前期SHR中已经观察到NTS中CO2刺激的心肺效应增强和ASIC1的上调.此外，在麻醉的成年SHR中，对ASIC1的特异性阻断有效地减弱了CO2刺激的NTS神经元放电速率的增加。NTS神经元侧脑室注射ASIC1a阻断剂PcTx1或敲除Asic1可显着降低CO2刺激的通气反应，并减少了CO2刺激的成人SHR动脉压和心率的增加。
结论：这些研究结果表明，NTS中的ASIC1信号传导失调导致了SHR中观察到的过度的CO2刺激心肺效应。
方法：通过全身体积描记术和遥测记录清醒大鼠的呼吸和血压，分别。Westernblot检测Wistar-Kyoto（WKY）大鼠和SHRNTS区ASIC1蛋白表达差异。通过细胞外记录评估NTS神经元的兴奋性。
结果：与WKY大鼠相比，在4周龄高血压前期SHR中已经观察到NTS中CO2刺激的心肺效应增强和ASIC1的上调.此外，在麻醉的成年SHR中，对ASIC1的特异性阻断有效地减弱了CO2刺激的NTS神经元放电速率的增加。NTS神经元侧脑室注射ASIC1a阻断剂PcTx1或敲除Asic1可显着降低CO2刺激的通气反应，并减少了CO2刺激的成人SHR动脉压和心率的增加。
结论：这些研究结果表明，NTS中的ASIC1信号传导失调导致了SHR中观察到的过度的CO2刺激心肺效应。
