Shanghai Key Laboratory of Bio-Crops, College of Life Science, Shanghai University, Shanghai, China.
Department of Physiology and Pathophysiology, Shanghai Medical College of Fudan University, Shanghai, China.
Hypertens Res. 2018 Dec;41(12):1013-1022. doi: 10.1038/s41440-018-0105-6. Epub 2018 Oct 4.
The rostral ventrolateral medulla (RVLM) plays a key role in mediating the development of stress-induced hypertension (SIH) by excitation and/or inhibition of sympathetic preganglionic neurons. The voltage-gated sodium channel Nav1.6 has been found to contribute to neuronal hyperexcitability. To examine the expression of Nav1.6 in the RVLM during SIH, a rat model was established by administering electric foot-shocks and noises. We found that Nav1.6 protein expression in the RVLM of SIH rats was higher than that of control rats, peaking at the tenth day of stress. Furthermore, we observed changes in blood pressure correlating with days of stress, with systolic blood pressure (SBP) found to reach a similarly timed peak at the tenth day of stress. Percentages of cells exhibiting colocalization of Nav1.6 with NeuN, a molecular marker of neurons, indicated a strong correlation between upregulation of Nav1.6 expression in NeuN-positive cells and SBP. The level of RSNA was significantly increased after 10 days of stress induction than control group. Compared with the SIHR, knockdown of Nav1.6 in RVLM of the SIHR decreased the level of SBP, heart rate (HR) and renal sympathetic nerve activity (RSNA). These results suggest that upregulated Nav1.6 expression within neurons in the RVLM of SIH rats may contribute to overactivation of the sympathetic system in response to SIH development.
延髓头端腹外侧区（RVLM）通过兴奋和/或抑制交感节前神经元在介导应激诱导性高血压（SIH）的发展中起着关键作用。已经发现电压门控钠离子通道 Nav1.6 有助于神经元过度兴奋。为了研究 SIH 期间 RVLM 中 Nav1.6 的表达，通过给予电脚刺激和噪声建立了大鼠模型。我们发现 SIH 大鼠 RVLM 中的 Nav1.6 蛋白表达高于对照组大鼠，在应激的第十天达到峰值。此外，我们观察到与应激天数相关的血压变化，收缩压（SBP）在应激的第十天达到类似的峰值。Nav1.6 与神经元分子标志物 NeuN 共定位的细胞百分比表明，NeuN 阳性细胞中 Nav1.6 表达的上调与 SBP 之间存在很强的相关性。与对照组相比，应激诱导 10 天后 RSNA 水平显著升高。与 SIHR 相比，SIHR 中 RVLM 中的 Nav1.6 敲低降低了 SBP、心率（HR）和肾交感神经活动（RSNA）的水平。这些结果表明，SIH 大鼠 RVLM 神经元中 Nav1.6 表达的上调可能有助于交感神经系统对 SIH 发展的过度激活。
