Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic Nerve Activity and Blood Pressure.
Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic Nerve Activity and Blood Pressure.
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DOI：
10.1161/hypertensionaha.116.08372
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Stocker SD
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文献类型：
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作者：
Kinsman BJ;Simmonds SS;Browning KN;Stocker SD
高盐饮食会提高脑脊液中的氯化钠浓度，从而增加盐敏感性高血压的交感神经活动（SNA）。终板血管器（OVLT）位于第三脑室的头端壁，缺乏完整的血脑屏障，在体液稳态中发挥着关键作用。因此，本研究采用多方面的方法来检查Sprague Dawley大鼠的OVLT神经元是否对细胞外氯化钠浓度的变化具有内在敏感性并介导对中枢氯化钠负荷的交感兴奋反应。使用体外全细胞记录，细胞外 NaCl 浓度 (2.5–10mM) 的逐步增加产生了 OVLT 神经元的浓度依赖性兴奋。此外，这些兴奋反应是 OVLT 神经元固有的，因为尽管药理突触阻断，高渗 NaCl 仍会诱发内向电流。体内单单位记录表明，大多数 OVLT 神经元 (72%, 13/19) 显示神经元向颈动脉内 (50μL/15 秒) 或脑室内输注 (5μL/10 分钟) 高渗 NaCl 的放电量呈浓度依赖性增加。将高渗 NaCl (30nL/60s) 微量注射到 OVLT 中，但不注射到邻近区域，以浓度依赖性方式增加腰椎 SNA、肾上腺 SNA 和 ABP。肾 SNA 下降，内脏 SNA 不受影响。最后，用 GABAA 受体激动剂蝇蕈醇 (24nL/10s) 局部抑制 OVLT 神经元，可显着减弱脑室内输注 0.5M 或 1.0M NaCl 的交感神经兴奋和升压反应。总的来说，这些发现表明 OVLT 神经元检测细胞外 NaCl 浓度的变化，从而选择性地改变 SNA 并升高 ABP。
High salt diet elevates NaCl concentrations in the cerebrospinal fluid to increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. The organum vasculosum of the lamina terminalis (OVLT) resides along the rostral wall of the third ventricle, lacks a complete blood-brain-barrier, and plays a pivotal role in body fluid homeostasis. Therefore, the present study used a multi-faceted approach to examine whether OVLT neurons of Sprague Dawley rats are intrinsically sensitive to changes in extracellular NaCl concentrations and mediate the sympathoexcitatory responses to central NaCl loading. Using in vitro whole-cell recordings, step-wise increases in extracellular NaCl concentrations (2.5–10mM) produced concentration-dependent excitation of OVLT neurons. Additionally, these excitatory responses were intrinsic to OVLT neurons as hypertonic NaCl evoked inward currents despite pharmacologic synaptic blockade. In vivo single-unit recordings demonstrate the majority of OVLT neurons (72%, 13/19) display concentration-dependent increases in neuronal discharge to intracarotid (50µL/15s) or intracerebroventricular infusion (5µL/10min) of hypertonic NaCl. Microinjection of hypertonic NaCl (30nL/60s) into the OVLT, but not adjacent areas, increased lumbar SNA, adrenal SNA, and ABP in a concentration-dependent manner. Renal SNA decreased, and splanchnic SNA remained unaffected. Finally, local inhibition of OVLT neurons with the GABAA receptor agonist muscimol (24nL/10s) significantly attenuated the sympathoexcitatory and pressor responses to intracerebroventricular infusion of 0.5M or 1.0M NaCl. Collectively, these findings indicate that OVLT neurons detect changes in extracellular NaCl concentrations to selectively alter SNA and raise ABP.