Blood pressure control by caudal ventrolateral medulla

通过尾部腹外侧延髓控制血压

• 批准号: 7224154
• 负责人: ANN M SCHREIHOFER
• 金额: $ 30.51万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-03 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224154
• 关键词: Affect; Area; Arts; Attenuated; Autonomic nervous system; Baroreflex; Brain; Brain Stem; Cardiovascular system; Cells; Chronic; Condition; Denervation; Figs - dietary; Glutamates; Goals; Hypertension; Hypothalamic structure; In Situ Hybridization; Inbred SHR Rats; Inbred WKY Rats; Label; Laboratories; Left; Link; Maintenance; Masks; Mediating; Messenger RNA; Methods; Modeling; Molecular; Nerve; Neuraxis; Neurons; Nucleus solitarius; Pathway interactions; Personal Satisfaction; Play; Pressoreceptors; Range; Rattus; Recording of previous events; Regulation; Research Personnel; Role; Site; Sympathetic Nervous System; Testing; Vasomotor; base; blood pressure regulation; extracellular; gamma-Aminobutyric Acid; midbrain central gray substance; normotensive; paraventricular nucleus; pressure; programs; response; restoration

DESCRIPTION (provided by applicant): The brain plays an important role in the regulation of arterial pressure (AP) via the autonomic nervous system. The long range goal of the applicant is to understand how the central nervous system (CNS) controls sympathetic vasomotor tone under conditions of normal AP and how the function is altered with hypertension. Many forms of hypertension are linked with elevated sympathetic nerve activity (SNA), although the basis of this sympatho-activation is not well understood. Normally, SNA is restrained by GABAergic neurons in the caudal ventrolateral medulla (CVLM) to maintain a consistent AP. For the short-term control of SNA and AP, these GABAergic CVLM neurons are an essential link in the central pathway for the baroreceptor reflex. However, GABAergic CVLM neurons also are clearly important for setting the long-term level of SNA independent of the baroreflex. We have observed that in the chronic absence of baroreceptor inputs or their site of termination in the nucleus tractus solitarius (NTS), the restoration of a normal mean AP is associated with a normal CVLM-mediated inhibition of SNA and AP. In contrast, spontaneously hypertensive rats have elevated SNA which may be linked with impaired CVLM-mediated inhibition of SNA and AP. Apart from baroreceptor inputs and the NTS, little is known about the central mechanisms regulating the activity of these powerful GABAergic CVLM neurons. This project will use a combination of state-of-the-art methods in rats (i.e. electrophysiological, neuroanatomical, and molecular approaches) to determine how other areas of the brain regulate the activity of GABAergic CVLM neurons under normotensive and hypertensive conditions. Specifically, we will determine whether identified glutamatergic inputs to the CVLM from the paraventricular nucleus of the hypothalamus and ventrolateral periaqueductal gray activate GABAergic CVLM neurons that project to the rostral ventrolateral medulla (RVLM). We will use chronic arterial baroreceptor denervated rats as a normotensive model to examine inputs to GABAergic CVLM neurons that may be masked by powerful baroreceptor inputs. In addition, we will determine whether the CVLM-mediated inhibition of SNA is impaired in spontaneously hypertensive rats. Collectively, these studies will provide a sophisticated analysis of the mechanisms underlying the brainstem's role in the long-term regulation of sympathetic vasomotor tone and AP and will determine functional changes that occur with chronic baroreceptor denervation and spontaneous hypertension.

描述（由申请人提供）：大脑通过自主神经系统在动脉压（AP）调节中发挥着重要作用。申请人的长期目标是了解中枢神经系统（CNS）在正常AP条件下如何控制交感血管舒缩张力以及该功能如何随着高血压而改变。许多形式的高血压与交感神经活动（SNA）升高有关，尽管这种交感神经活动的基础尚不清楚。通常，SNA 受到尾侧腹外侧髓质 (CVLM) 中 GABA 能神经元的抑制，以维持一致的 AP。对于 SNA 和 AP 的短期控制，这些 GABA 能 CVLM 神经元是压力感受器反射中央通路中的重要环节。然而，GABA 能 CVLM 神经元对于设置独立于压力反射的 SNA 长期水平显然也很重要。我们观察到，在孤束核 (NTS) 长期缺乏压力感受器输入或其终止位点的情况下，正常平均 AP 的恢复与正常 CVLM 介导的 SNA 和 AP 抑制相关。相反，自发性高血压大鼠的 SNA 升高，这可能与 CVLM 介导的 SNA 和 AP 抑制受损有关。除了压力感受器输入和 NTS 之外，人们对调节这些强大的 GABA 能 CVLM 神经元活动的中心机制知之甚少。该项目将在大鼠身上结合使用最先进的方法（即电生理学、神经解剖学和分子方法）来确定大脑其他区域在正常血压和高血压条件下如何调节 GABA 能 CVLM 神经元的活动。具体来说，我们将确定从下丘脑室旁核和腹外侧导水管周围灰质向 CVLM 的谷氨酸能输入是否激活投射到延髓头端腹外侧 (RVLM) 的 GABA 能 CVLM 神经元。我们将使用慢性动脉压力感受器去神经支配的大鼠作为血压正常模型来检查可能被强大的压力感受器输入掩盖的 GABA 能 CVLM 神经元的输入。此外，我们将确定 CVLM 介导的 SNA 抑制在自发性高血压大鼠中是否受损。总的来说，这些研究将对脑干在交感血管舒缩张力和 AP 的长期调节中的作用机制进行复杂的分析，并将确定慢性压力感受器去神经支配和自发性高血压所发生的功能变化。