Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.
Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.
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DOI：
10.1161/hypertensionaha.115.05936
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Farquhar WB
中科院分区：
文献类型：
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作者：
Stocker SD;Lang SM;Simmonds SS;Wenner MM;Farquhar WB
脑脊液（CSF）中NaCl浓度升高会增加盐敏感性高血压患者的交感神经活动（SNA）。延髓头端腹外侧区（RVLM）的神经元在SNA的调节中起着关键作用，并接受来自对高钠血症有反应的几个下丘脑结构的单突触或多突触输入。因此，本研究探讨了RVLM神经元对SNA和CSF高钠血症升压反应的贡献。侧心室输注0.15 M、0.6 M和1.0 M NaCl（5µL/10 min）可导致腰部SNA、肾上腺SNA和动脉血压（ABP）呈浓度依赖性增加，尽管内脏SNA无变化且肾脏SNA下降。神经节阻滞与氯异松达明或急性病变的终板阻断或显着减弱这些反应，分别。RVLM微量注射GABAA激动剂蝇蕈醇可阻断ICV灌注1 M NaCl引起的交感兴奋反应。此外，离子型谷氨酸受体的阻滞剂，而不是血管紧张素II 1型，显著减弱了腰SNA，肾上腺SNA和ABP的增加。最后，脊髓投射RVLM神经元的单单位记录揭示了三个不同的群体的基础上ICV输注1 M NaCl的放电反应：I型兴奋（46%，11/24），II型抑制（37%，9/24），和III型无变化（17%，4/24）。所有传导速度慢的神经元均为I型细胞。总的来说，这些发现表明，CSF NaCl浓度的急性增加通过谷氨酸受体激活选择性地激活RVLM神经元的离散群体，以增加SNA和ABP。
Elevated NaCl concentrations of the cerebrospinal fluid (CSF) increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or poly-synaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to CSF hypernatremia. Lateral ventricle infusion of 0.15M, 0.6M, and 1.0M NaCl (5µL/10 min) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure (ABP) despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the GABAA agonist muscimol abolished the sympathoexcitatory response to ICV infusion of 1M NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and ABP. Finally, single-unit recordings of spinally-projecting RVLM neurons revealed three distinct populations based on discharge responses to ICV infusion of 1M NaCl: Type I excited (46%, 11/24), Type II inhibited (37%, 9/24), and Type III no change (17%, 4/24). All neurons with slow conduction velocities were Type I cells. Collectively, these findings suggest that acute increases in CSF NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and ABP.