Contribution of retrotrapezoid nucleus neurons to CO2-amplified cardiorespiratory activity in spontaneously hypertensive rats
Contribution of retrotrapezoid nucleus neurons to CO2-amplified cardiorespiratory activity in spontaneously hypertensive rats
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梯形后核神经元对自发性高血压大鼠 CO2 放大心肺活动的贡献
DOI：
10.1113/jp280246
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Tian Y;Geng D;Wang Y;Shi L;Yu H;He W;Zhu Y;Jun S;Fu C;Wang X;Zhang X;Yuan F;Wang S
心血管活动的呼吸调节对于维持有效的通气和灌注比是必不可少的。中枢呼吸化学感受器的激活不仅激发呼吸反应，而且调节交感神经活动和动脉血压（ABP）。后斜方核（RTN）是中枢呼吸化学感受器中特征最完整的一簇。我们假设RTN神经元有助于增强CO2刺激的呼吸和心血管反应在成年自发性高血压大鼠（SHR）。我们的研究结果表明，自发性高血压大鼠表现出增强的高碳酸血症的心肺反应比年龄匹配的血压正常的Wistar-Kyoto大鼠。RTN神经元的基因消融显著抑制了SHR的高碳酸血症性反应（HCVR），并消除了CO2刺激的ABP和心率的更大增加。此外，SHR RTN中pH敏感性通道蛋白水平较高，包括ASK-2通道、Kv12.1通道和酸敏感离子通道3。氯非铵（i. p.）给药，ASK-2通道的非选择性抑制剂，不仅显著降低了HCVR的增强，而且还抑制了SHR中ABP和心率的CO2放大增加。此外，Clofilium显着减少CO 2激活的RTN神经元的数量在SHR。总之，我们认为RTN神经元在增强SHR的高碳酸血症和心血管反应中起重要作用，并且所涉及的假定机制与RTN中的ASK-2通道活性相关。
The respiratory regulation of cardiovascular activity is essential for maintaining efficient ventilation and perfusion ratio. Activation of central respiratory chemoreceptors not only elicits a ventilatory response but also regulates sympathetic nerve activity and arterial blood pressure (ABP). The retrotrapezoid nucleus (RTN) is the most completely characterized cluster of central respiratory chemoreceptors. We hypothesize that RTN neurons contribute to augmented CO2-stimulated respiratory and cardiovascular responses in adult spontaneously hypertensive rats (SHRs). Our findings indicate that SHRs exhibit enhanced hypercapnic cardiorespiratory responses than age-matched normotensive Wistar–Kyoto rats. Genetic ablation of RTN neurons notably depresses an enhanced hypercapnic ventilatory response (HCVR) and eliminates CO2-stimulated greater increase in ABP and heart rate in SHRs. In addition, SHRs have higher protein level of pH-sensitive channels in the RTN, including TASK-2 channels, Kv12.1 channels and acid-sensing ion channel 3. Administration of clofilium (i.p.), an unselective inhibitor of TASK-2 channels, not only significantly reduces the enhanced HCVR but also inhibits CO2-amplified increases in ABP and heart rate in SHRs. Moreover, clofilium significantly decreases the number of CO2-activated RTN neurons in SHRs. Taken together, we suggest that RTN neurons play an important role in enhanced hypercapnic ventilatory and cardiovascular responses in SHRs and the putative mechanism involved is associated with TASK-2 channel activity in the RTN.