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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，外周来源的血管紧张素可以刺激中枢神经系统中启动代偿反应的受体体液流失。这些包括动脉压升高，血管加压素解脱，解渴。研究表明，神经元结构位于前腹侧第三脑室(AV3V)区是必要的用于检测外周降压素。这些相同的结构是也与脑源性血管紧张素的渗透接收和感觉有关。最近的解剖学研究假设血管紧张素，也许穹隆下器(SFO)和血管细胞器中的渗透压受体终板(OVLT)向核内发送兴奋性神经输入内侧核(NM)激活上述代偿机制。对以下项目感兴趣研究表明，这些结构的破坏这个区域可以预防一些实验性的高血压，并且改变了脑血管紧张素水平和神经元敏感性这一区域在自发性高血压大鼠中被发现。然而，到目前为止，对神经生理学方面的相互联系知之甚少。这些结构。在过去的两年里，我们的学习集中在位于OVLT区的血管紧张素II敏感神经元。这提案是该项目的继续，在该项目中，我们将扩大我们的研究内部互连的电生理学 AV3V区。利用新近研制的AV3V体外脑片将研究SFO和OVLT刺激对NM神经元的影响。使用这种方法，我们将仔细检查神经药理学这些投射，其中一些是血管紧张素能的。使用完整的准备工作，我们还将描述SFO、OVLT和NM的影响视上核(SON)和室旁核(PVN)的激活大细胞和小细胞神经元。在另一系列实验中，将检查NM中的神经元活动的敏感性和药理学之后的上升心血管信息的整合动脉压的改变和直接电激活传入神经。拟议的研究的目的是开始一项仔细的神经元的电生理学和药理学研究位于AV3V区的构造，集中在假设的血管紧张素能通路。这些研究的结果应该提供关于动脉压神经调节的重要新信息和流体平衡，以及有关函数的更多一般信息中枢多肽能通路。