Division of Integrative Physiology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Am J Physiol Heart Circ Physiol. 2020 Dec 1;319(6):H1197-H1207. doi: 10.1152/ajpheart.00273.2020. Epub 2020 Sep 18.
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 ( = 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 ( = 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 ( = 9) but not in sham-operated Jaws rats ( = 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. Using 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.
心力衰竭（HF）中观察到的交感血管运动张力升高可能涉及投射到延髓头侧腹外侧区（RVLM）神经元的下丘脑室旁核神经元的功能障碍。本研究旨在阐明 RVLM 神经元在心肌梗死（MI）后维持静息肾交感神经活动（RSNA）中的作用。在雄性大鼠中，慢性结扎左冠状动脉以诱导 MI。大鼠接受编码archaerhodopsin T（ArchT）的腺相关病毒（AAV）载体的 PVN 微注射，该载体带有报告黄色荧光蛋白（eYFP）。ArchT 大鼠的 RVLM 中具有丰富的 eYFP 标记的、源自 PVN 的轴突分布。在接受 MI 的麻醉 ArchT 大鼠（n = 12）中，通过 RVLM 中的 532nm 波长激光照射实现的 PVN-RVLM 通路的光遗传抑制显著降低了 RSNA。在 sham 手术的 ArchT 大鼠中未发现这种效应（n = 6）。其他大鼠组接受逆行 AAV 载体的 RVLM 微注射，该载体编码红光驱动的 halorhodopsin Jaws（Jaws），带有报告绿色荧光蛋白（GFP），并显示 GFP 标记的胞体和树突在 PVN 中表达。在 635nm 波长下，PVN 的激光照射在 MI 的 Jaws 大鼠中引起显著的肾交感神经抑制（n = 9），但在 sham 手术的 Jaws 大鼠中没有（n = 8）。这些结果表明，MI 后来自 PVN-RVLM 神经元的交感兴奋传入增强，表明该单突触通路是中枢神经系统回路的一部分，在产生 HF 中常见的升高的交感血管运动张力中起关键作用。使用大鼠的光遗传学，我们报告说，投射到延髓头侧腹外侧区的下丘脑室旁核神经元的交感兴奋传入在心肌梗死后增强。提示该单突触通路构成了心力衰竭中常见的交感神经过度激活的中枢神经系统回路的关键部分。
