ROLE OF CENTRAL ALL-SENSITIVE NEURONS IN HYPERTENSION

中枢全敏感神经元在高血压中的作用

基本信息

批准号：
3340216
负责人：
DOUGLAS O NELSON
金额：
$ 9.05万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-08-01 至 1988-11-30
项目状态：
已结题

项目摘要

Numerous studies show that angiotensin of peripheral origin stimulates receptors in the central nervous system to initiate compensatory reactions to fluid loss. These include increased arterial pressure, vasopressin release, and thirst. Investigations indicate that neuronal structures located in the anterior ventral third ventricle (AV3V) region are necessary for the detection of peripheral anqiotensin. These same structures are also implicated in osmoreception and sensing of brain-borne angiotensin. Recent anatomical studies postulate that angiotensin, and perhaps osmoreceptors, in the subfornical organ (SFO) and the organum vasculosum lamina terminalis (OVLT) send excitatory neural input to the nucleus medianus (NM) to mobolize the above compensatory mechanisms. Interest in these structures has been heightened by studies showing that destruction of this region prevents a number of experimental forms of hypertension, and that altered brain angiotensin levels and neuronal sensitivity in this region are found in the spontaneously hypertensive rat. To date, however, little is known of the neurophysiology of the interconnections between these structures. During the past two years our studies have concentrated on angiotensin II sensitive neurons located in the OVLT region. This proposal is a continuation of that project in which we will expand our studies to investigate the electrophysiology of interconnections within the AV3V region. Utilizing a recently developed AV3V in vitro brain slice we will investigate the affects of SFO and OVLT stimulation on NM neurons. Using this approach we will carefully examine the neuropharmacology of these projections, some of which are angiotensinergic. Using intact preparations, we will also characterize the influence of SFO, OVLT and NM activation on identified supraoptic (SON) and paraventricular (PVN) nucleus magnocellular and parvocellular neurons. In another series of experiments, neuronal activity in the NM will be examined for sensitivity and integration of ascending cardiovascular information following pharmacologic alterations in arterial pressure and direct electrical activation of afferent nerves. The purpose of the proposed study is to begin a careful electrophysiologic and pharmacological investigation of the neuronal structures located in the AV3V region, concentrating on postulated angiotensinergic pathways. The results of these studies should provide important new information about the neural regulation of arterial pressure and fluid balance, as well as, more general information about the function of central peptidergic pathways.

大量研究表明，周围起源的血管紧张素会刺激中枢神经系统中的受体发起补偿反应流体损失。这些包括增加动脉压加压素释放和口渴。研究表明神经元结构位于前腹侧第三心室（AV3V）区域是必要的用于检测周围拟南芥。这些相同的结构是还与脑传播血管紧张素的渗透感和传感有关。最近的解剖学研究假设血管紧张素，也许肌肉受体，在副骨器器官（SFO）和细胞器Vasculosum中 Lamina末端（OVLT）向细胞核发送兴奋性神经输入 MEDIANUS（NM）动员上述补偿机制。感兴趣这些结构通过研究表明破坏该区域防止多种实验形式的高血压，并且这改变了脑血管紧张素水平和神经元敏感性在自发的高血压大鼠中发现了区域。但是，迄今为止关于互连的神经生理学知之甚少这些结构。在过去的两年中，我们的研究集中了在OVLT区域的血管紧张素II敏感神经元上。这提案是该项目的延续，我们将扩大我们的研究研究中互连的电生理学 AV3V地区。利用最近开发的AV3V体外脑切片我们将研究SFO和OVLT刺激对NM神经元的影响。使用这种方法，我们将仔细检查这些预测，其中一些是血管紧力的。使用完整准备工作，我们还将表征SFO，OVLT和NM的影响对鉴定的上（SON）和室室（PVN）核激活大细胞和副细胞神经元。在另一个系列实验中， NM中的神经元活性将检查敏感性和药理学后的升级心血管信息的整合动脉压的改变和直接电动激活传入神经。拟议的研究的目的是开始谨慎神经元的电生理学和药理研究位于AV3V区域的结构，集中于假定血管紧张素能途径。这些研究的结果应提供有关动脉压神经调节的重要新信息和流体平衡，以及有关功能的更多一般信息中央替代途径。