ROLE OF CENTRAL ALL-SENSITIVE NEURONS IN HYPERTENSION

中枢全敏感神经元在高血压中的作用

• 批准号: 3340214
• 负责人: DOUGLAS O NELSON
• 金额: $ 9.83万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/3340214
• 关键词: alpha adrenergic agent; angiotensin /renin /aldosterone hypertension; angiotensin II; body fluid osmolarity; cellular pathology; centrally acting drug; electrolyte balance; familial hypertension; hippocampus; hypothalamus; interneurons; membrane potentials; neuroanatomy; neurons; neuropharmacology; neurophysiology; neurotoxins; single cell analysis

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刺激 受体在中枢神经系统启动补偿反应 到体液流失 包括动脉压升高，加压素 释放，口渴。 研究表明，神经元结构 位于第三脑室前腹侧（AV3V）区域的 用于检测外周血管紧张素。 这些相同的结构是 还涉及脑源性血管紧张素的受体和感受。 最近的解剖学研究假设，血管紧张素， 穹窿下器（SFO）和血管器中的β受体 终板（OVLT）将兴奋性神经输入送到核团 正中肌（NM），使上述代偿机制运动化。 兴趣 研究表明，这些结构的破坏 该区域可预防多种实验性高血压， 改变了大脑血管紧张素水平和神经元的敏感性， 区域中发现的自发性高血压大鼠。 然而，迄今为止， 对于神经生理学中的神经元之间的相互联系知之甚少， 这些结构。 在过去的两年里，我们的研究集中在 血管紧张素II敏感神经元位于OVLT区域。 这 该建议是我们将扩大 研究，以调查电生理学的互连内， AV3V区。 利用最近开发的AV3V体外脑切片， 将研究SFO和OVLT刺激对NM神经元的影响。 使用这种方法，我们将仔细研究神经药理学的 这些突起，其中一些是血管紧张素能的。 使用完整 准备，我们还将表征SFO，OVLT和NM的影响 视上核（SON）和室旁核（PVN）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， 整合药理学后的心血管信息 动脉压的改变和直接电激活 传入神经。 拟议研究的目的是开始一项认真的 神经元的电生理学和药理学研究 位于AV3V区域的结构，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 关于神经调节动脉压的重要新信息 和液体平衡，以及有关功能的更多一般信息 中枢肽能通路的一部分。