Sympathoexcitatory input from hypothalamic paraventricular nucleus neurons projecting to rostral ventrolateral medulla is enhanced after myocardial infarction
Sympathoexcitatory input from hypothalamic paraventricular nucleus neurons projecting to rostral ventrolateral medulla is enhanced after myocardial infarction
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心肌梗塞后下丘脑室旁核神经元投射到延髓头侧腹外侧的交感兴奋输入增强
DOI：
10.1152/ajpheart.00273.2020
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发表时间：
2020
影响因子：
4.8
通讯作者：
Watanabe Tatsuo
中科院分区：
文献类型：
--
作者：
Koba Satoshi;Hanai Eri;Kumada Nao;Watanabe Tatsuo
在心力衰竭（HF）中观察到的交感神经血管紧张素升高可能涉及投射到延髓头端腹外侧区的下丘脑室旁核神经元（PVN-RVLM神经元）的功能障碍。本研究旨在阐明PVN-RVLM神经元在心肌梗死（MI）后静息肾交感神经活动（RSNA）维持中的作用。在雄性大鼠中，长期结扎左冠状动脉以诱导MI。大鼠接受PVN显微注射腺相关病毒（AAV）载体编码古视紫红质T（ArchT）与报告黄色荧光蛋白（eYFP）。ArchT大鼠RVLM中有丰富的eYFP标记的PVN来源的轴突分布。在患有MI的麻醉ArchT大鼠（n= 12）中，通过532 nm波长激光照射RVLM实现PVN-RVLM通路的光遗传学抑制显著降低RSNA。在假手术ArchT大鼠中未发现这种效应（n= 6）。其他大鼠组接受编码红光可驱动的盐视紫红质Jaws（Jaws）和报告基因绿色荧光蛋白（GFP）的逆行AAV载体的RVLM显微注射，并显示GFP标记的细胞体和树突在PVN中表达。635 nm波长的PVN激光照射引起MI的Jaws大鼠（n= 9）显著的肾交感神经抑制，但在假手术的Jaws大鼠（n= 8）中没有。这些结果表明，来自PVN-RVLM神经元的交感兴奋性输入在MI后增强，这表明该单突触通路是中枢神经系统回路的一部分，其在产生HF常见的升高的交感血管紧张素中起关键作用。我们报道了下丘脑室旁核神经元投射到延髓头端腹外侧区的交感神经兴奋性输入增强，心肌梗死这表明，这种单突触通路构成了中枢神经系统回路的关键部分，交感神经过度激活常见于心力衰竭。
Elevated sympathetic vasomotor tone seen in heart failure (HF) may involve dysfunction of the hypothalamic paraventricular nucleus neurons that project to the rostral ventrolateral medulla (PVN-RVLM neurons). This study aimed to elucidate the role of PVN-RVLM neurons in the maintenance of resting renal sympathetic nerve activity (RSNA) after myocardial infarction (MI). In male rats, the left coronary artery was chronically ligated to induce MI. The rats received PVN microinjections of an adeno-associated viral (AAV) vector encoding archaerhodopsin T (ArchT) with the reporter yellow fluorescence protein (eYFP). The ArchT rats had abundant distributions of eYFP-labeled, PVN-derived axons in the RVLM. In anesthetized ArchT rats with MI (n= 12), optogenetic inhibition of the PVN-RVLM pathway achieved by 532-nm-wavelength laser illumination to the RVLM significantly decreased RSNA. This effect was not found in sham-operated ArchT rats (n= 6). Other rat groups received RVLM microinjections of a retrograde AAV vector encoding the red light-drivable halorhodopsin Jaws (Jaws) with the reporter green fluorescence protein (GFP) and showed expression of GFP-labeled cell bodies and dendrites in the PVN. Laser illumination of the PVN at a 635 nm wavelength elicited significant renal sympathoinhibition in Jaws rats with MI (n= 9) but not in sham-operated Jaws rats (n= 8). These results indicate that sympathoexcitatory input from PVN-RVLM neurons is enhanced after MI, suggesting that this monosynaptic pathway is part of the central nervous system circuitry that plays a critical role in generating an elevated sympathetic vasomotor tone commonly seen with HF.NEW & NOTEWORTHYUsing optogenetics in rats, we report that sympathoexcitatory input from hypothalamic paraventricular nucleus neurons that project to the rostral ventrolateral medulla is enhanced after myocardial infarction. It is suggested that this monosynaptic pathway makes up a key part of central nervous system circuitry underlying sympathetic hyperactivation commonly seen in heart failure.