*Department of Physiology II, Kanazawa Medical University, Uchinada, Japan †Department of Colorectal and Hernia Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China ‡Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki, Japan §Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan ||Department of Infectious Disease, The Sheng Jing Hospital of China Medical University, Shenyang, China.
Shock. 2017 Nov;48(5):576-582. doi: 10.1097/SHK.0000000000000889.
The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves.
RSNA, HR, and mean systemic arterial pressure were continuously measured in male pentobarbital-anesthetized C57BL/6N mice. Hemorrhagic hypotension of 50 mmHg was evoked and maintained for 10 min.
During hemorrhagic hypotension, RSNA initially increased and then sustainedly decreased, while HR progressively decreased. Vagotomy eliminated the second-phase sympathoinhibition and bradycardia, and carotid sinus denervation with vagotomy abolished the initial renal sympathoexcitation. The renal sympathoinihibition during hemorrhagic hypotension of 50 mmHg was eliminated in mice pretreated with a transient receptor potential vanilloid type 1 channel (TRPV1) inhibitor, capsazepine, and in TRPV1 knockout (TRPV1) mice, but not in TRPV4 knockout mice. The bradycardia response to hemorrhagic hypotension was also absent in TRPV1 mice and mice pretreated with capsazepine.
Hemorrhagic hypotension in anesthetized mice causes biphasic responses of RSNA with an initial increase, followed by a sustained decrease, and a progressive decrease in HR. The initial sympathoexcitation is mediated by carotid sinus baroreceptors, while the later sympathoinhibition and bradycardia are mediated via the TRPV1 signals of vagal afferents.
在麻醉大鼠中，肾交感神经活动（RSNA）和心率（HR）对持续性失血性休克的抑制反应已经得到确定，但在小鼠中尚未确定。在这里，我们研究了麻醉小鼠中 RSNA 和 HR 对失血性低血压的反应，重点研究了传入迷走神经的分子基础机制在其中的作用。
在雄性戊巴比妥麻醉的 C57BL/6N 小鼠中连续测量 RSNA、HR 和平均系统动脉压。诱发并维持 50mmHg 的失血性低血压 10min。
在失血性低血压期间，RSNA 最初增加，然后持续减少，而 HR 逐渐降低。迷走神经切断术消除了第二期的交感神经抑制和心动过缓，颈动脉窦神经切断术加迷走神经切断术消除了初始的肾交感神经兴奋。用瞬时受体电位香草酸类型 1 通道（TRPV1）抑制剂辣椒素预处理的小鼠以及 TRPV1 敲除（TRPV1）小鼠中，50mmHg 失血性低血压期间的肾交感神经抑制作用被消除，但在 TRPV4 敲除小鼠中没有消除。TRPV1 小鼠和用辣椒素预处理的小鼠中，失血性低血压引起的心动过缓反应也不存在。
麻醉小鼠的失血性低血压引起 RSNA 的双相反应，初始增加，随后持续减少，HR 逐渐减少。初始的交感神经兴奋是由颈动脉窦压力感受器介导的，而后期的交感神经抑制和心动过缓是通过迷走神经传入的 TRPV1 信号介导的。
