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 an archaerhodopsin T (ArchT) with the reporter eYFP. The ArchT rats had abundant distributions of eYFP‒labelled, 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_rg) with the reporter GFP, and showed expression of GFP‒labelled cell bodies and dendrites in the PVN. Laser illumination of the PVN at a 635‒nm‒wavelength elicited significant renal sympathoinhibition in Jaws_rg rats with MI (n = 9) but not in sham‒operated Jaws_rg 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 elevated sympathetic vasomotor tone commonly seen with HF.

中文翻译：

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心肌梗塞后，下丘脑室旁核神经元投射到延髓腹侧延髓的交感兴奋输入增加。

心力衰竭（HF）中见到的交感性血管舒缩张力升高可能涉及下丘脑室旁核神经元功能失调，该神经元投射到延髓腹侧延髓（PVN‒RVLM神经元）。这项研究旨在阐明PVN‒RVLM神经元在心肌梗死（MI）后维持静止的肾交感神经活动（RSNA）中的作用。在雄性大鼠中，慢性结扎左冠状动脉以诱发心肌梗死。大鼠用报告基因eYFP进行腺病毒相关病毒（AAV）载体的PVN显微注射，该载体编码古细菌视紫红质T（ArchT）。ArchT大鼠在RVLM中具有丰富的eYFP‒标记的，PVN‒衍生的轴突分布。在麻醉的具有MI（n = 12）的ArchT大鼠中，532‒nm‒波长激光照射到RVLM对PVN‒RVLM途径的光遗传抑制显着降低了RSNA。在假手术的ArchT大鼠（n = 6）中未发现这种作用。其他大鼠组接受RVLM显微注射，该逆转录AAV载体编码红光可驱动的视紫红质大颚（Jaws）_rg）与报告GFP，并显示GFP showed标记的细胞体和树突在PVN中的表达。PVN在635‒nm‒波长处的激光照射在MI的Jaws _rg大鼠（n = 9）中引起显着的肾脏交感神经抑制，而在假手术的Jaws _rg大鼠（n = 8）中则没有。这些结果表明，MI后，PVNLMRVLM神经元的交感神经兴奋性输入增强，表明该单突触通路是中枢神经系统电路的一部分，在产生HF常见的升高的交感性血管舒缩张力中起关键作用。