Activation of the Organum Vasculosum of the Lamina Terminalis Produces a Sympathetically Mediated Hypertension.
Activation of the Organum Vasculosum of the Lamina Terminalis Produces a Sympathetically Mediated Hypertension.
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DOI：
10.1161/hypertensionaha.121.18117
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Browning KN
中科院分区：
文献类型：
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作者：
Stocker SD;Wenner MM;Farquhar WB;Browning KN
终板血管器（OVLT）中的神经元感知细胞外NaCl和血管紧张素II浓度以调节体液稳态和动脉血压（ABP）。第三脑室前腹侧区或OVLT的损伤可减轻多种形式的神经源性高血压。然而，OVLT神经元直接调节交感神经活动（SNA）产生高血压的程度尚不清楚。因此，本研究通过使用多方面的方法来验证这一假设，包括光遗传学，单单位和多纤维神经记录以及化学遗传学。首先，在清醒的Sprague-Dawley大鼠（250- 400 g）中OVLT神经元的光遗传学激活产生ABP和心率的频率依赖性增加。加压素受体拮抗剂[β-巯基-β，β-环戊亚甲基丙酰1，O-me-Tyr 2，Arg 8]-加压素不改变这些反应，但可被神经节阻滞剂氯异山达明消除。第二，OVLT神经元的光遗传学激活显著升高肾、内脏和腰椎SNA。第三，单单位记录显示OVLT的光遗传激活显著增加延髓头端腹外侧区的球脊髓交感神经元的放电。最后，OVLT神经元的慢性化学激活7天显著增加24小时液体摄入量和平均ABP。当24小时的液体摄入量被钳制在基线摄入量，OVLT神经元的化学发生激活仍然产生了类似的增加ABP。神经节阻滞剂氯异松达明评估的神经源性升压活动在OVLT激活7天时比基线更大。总的来说，这些发现表明，急性或慢性激活OVLT神经元产生交感神经介导的高血压。
Neurons in the organum vasculosum of the lamina terminalis (OVLT) sense extracellular NaCl and angiotensin II concentrations to regulate body fluid homeostasis and arterial blood pressure (ABP). Lesion of the anteroventral third ventricular region or OVLT attenuates multiple forms of neurogenic hypertension. However, the extent by which OVLT neurons directly regulate sympathetic nerve activity (SNA) to produce hypertension is not known. Therefore, the present study tested this hypothesis by using a multi-faceted approach including optogenetics, single-unit and multi-fiber nerve recordings, and chemogenetics. First, optogenetic activation of OVLT neurons in conscious Sprague-Dawley rats (250–400g) produced frequency-dependent increases in ABP and heart rate. These responses were not altered by the vasopressin receptor antagonist [β-mercapto-β,β-cyclopentamethylenepropionyl1,O-me-Tyr2,Arg8]-vasopressin but eliminated by the ganglionic blocker chlorisondamine. Second, optogenetic activation of OVLT neurons significantly elevated renal, splanchnic, and lumbar SNA. Third, single-unit recordings revealed optogenetic activation of the OVLT significantly increased the discharge of bulbospinal, sympathetic neurons in the rostral ventrolateral medulla. Lastly, chronic chemogenetic activation of OVLT neurons for 7 days significantly increased 24-h fluid intake and mean ABP. When the 24-h fluid intake was clamped at baseline intakes, chemogenetic activation of OVLT neurons still produced a similar increase in ABP. Neurogenic pressor activity assessed by the ganglionic blocker chlorisondamine was greater at 7 days of OVLT activation versus baseline. Collectively, these findings indicate that acute or chronic activation of OVLT neurons produces a sympathetically-mediated hypertension.