NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure
NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure
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DOI：
10.1113/jp274537
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发表时间：
2017-09-15
影响因子：
5.5
通讯作者：
Stocker, Sean D.
中科院分区：
文献类型：
--
作者：
Kinsman, Brian J.;Browning, Kirsteen N.;Stocker, Sean D.
关键点细胞外渗透压的变化刺激口渴和加压素分泌通过中枢神经元受体;然而，高渗NaCl的中枢输注比高渗甘露醇/山梨醇的输注产生更大的交感神经兴奋和升压反应。终板血管器（OVLT）中的神经元感知细胞外渗透压和NaCl的变化。在这项研究中，我们发现，脑室内灌注或局部OVLT注射高渗NaCl增加腰交感神经活动，肾上腺交感神经活动和动脉血压，而等渗甘露醇/山梨醇没有改变任何variable.In体外全细胞记录表明，大多数OVLT神经元高渗NaCl或甘露醇。然而，高渗NaCl刺激放电频率的增加比等渗甘露醇更大。颈动脉或侧脑室灌注高渗NaCl比等渗山梨醇引起OVLT神经元放电频率更大的增加。总的来说，这些新的数据表明，OVLT神经元的子集不同的反应高渗NaCl与渗透压，随后调节体液稳态。这些反应可能反映了不同的细胞机制下的NaCl-与NaCl-sensing.Systemic或中枢灌注高渗NaCl和其他渗透容易刺激口渴和加压素分泌。相比之下，高渗NaCl的中心输注产生的动脉血压（ABP）的增加大于等渗甘露醇/山梨醇。虽然这些反应取决于神经元的血管器的终板（OVLT），这些观察表明OVLT神经元可能会感觉到或不同的反应，高渗氯化钠与渗透压。本研究的目的是在Sprague-Dawley大鼠中检验这一假设。首先，侧脑室（icv）注入1.0mNaCl（5l/10 min）比等渗山梨醇（2.0osmoll（-1））能显著增加腰交感神经活动（SNA）、肾上腺SNA和ABP。第二，OVLT微量注射1.0mNaCl（20 nl）显著提高腰SNA、肾上腺SNA和ABP。等渗山梨醇未改变任何变量。第三，体外全细胞记录显示，50%（18/36）的OVLT神经元显示对高渗NaCl（+7.5mm）和甘露醇（+15mm）的放电增加。在这些神经元中，56%（10/18）的神经元对高渗NaCl的放电反应比甘露醇更强。第四，在体内单单位记录显示，颈动脉注射高渗NaCl产生的OVLT细胞放电，腰SNA和ABP的浓度依赖性增加。等渗输注高渗山梨醇的反应显着较小。最后，icv输注0.5M NaCl比icv输注等渗山梨醇显著增加OVLT放电和ABP。总的来说，这些研究结果表明，NaCl和渗透刺激产生不同的反应OVLT神经元，并可能代表不同的细胞过程来调节口渴，加压素分泌和自主神经功能。
Key pointsChanges in extracellular osmolarity stimulate thirst and vasopressin secretion through a central osmoreceptor; however, central infusion of hypertonic NaCl produces a greater sympathoexcitatory and pressor response than infusion of hypertonic mannitol/sorbitol. Neurons in the organum vasculosum of the lamina terminalis (OVLT) sense changes in extracellular osmolarity and NaCl. In this study, we discovered that intracerebroventricular infusion or local OVLT injection of hypertonic NaCl increases lumbar sympathetic nerve activity, adrenal sympathetic nerve activity and arterial blood pressure whereas equi-osmotic mannitol/sorbitol did not alter any variable.In vitro whole-cell recordings demonstrate the majority of OVLT neurons are responsive to hypertonic NaCl or mannitol. However, hypertonic NaCl stimulates a greater increase in discharge frequency than equi-osmotic mannitol. Intracarotid or intracerebroventricular infusion of hypertonic NaCl evokes a greater increase in OVLT neuronal discharge frequency than equi-osmotic sorbitol. Collectively, these novel data suggest that subsets of OVLT neurons respond differently to hypertonic NaCl versus osmolarity and subsequently regulate body fluid homeostasis. These responses probably reflect distinct cellular mechanisms underlying NaCl- versus osmo-sensing.Systemic or central infusion of hypertonic NaCl and other osmolytes readily stimulate thirst and vasopressin secretion. In contrast, central infusion of hypertonic NaCl produces a greater increase in arterial blood pressure (ABP) than equi-osmotic mannitol/sorbitol. Although these responses depend on neurons in the organum vasculosum of the lamina terminalis (OVLT), these observations suggest OVLT neurons may sense or respond differently to hypertonic NaCl versus osmolarity. The purpose of this study was to test this hypothesis in Sprague-Dawley rats. First, intracerebroventricular (icv) infusion (5l/10min) of 1.0m NaCl produced a significantly greater increase in lumbar sympathetic nerve activity (SNA), adrenal SNA and ABP than equi-osmotic sorbitol (2.0osmoll(-1)). Second, OVLT microinjection (20nl) of 1.0m NaCl significantly raised lumbar SNA, adrenal SNA and ABP. Equi-osmotic sorbitol did not alter any variable. Third, in vitro whole-cell recordings demonstrate that 50% (18/36) of OVLT neurons display an increased discharge to both hypertonic NaCl (+7.5mm) and mannitol (+15mm). Of these neurons, 56% (10/18) displayed a greater discharge response to hypertonic NaCl vs mannitol. Fourth, in vivo single-unit recordings revealed that intracarotid injection of hypertonic NaCl produced a concentration-dependent increase in OVLT cell discharge, lumbar SNA and ABP. The responses to equi-osmotic infusions of hypertonic sorbitol were significantly smaller. Lastly, icv infusion of 0.5m NaCl produced significantly greater increases in OVLT discharge and ABP than icv infusion of equi-osmotic sorbitol. Collectively, these findings indicate NaCl and osmotic stimuli produce different responses across OVLT neurons and may represent distinct cellular processes to regulate thirst, vasopressin secretion and autonomic function.