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.
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。