Blood pressure control by caudal ventrolateral medulla

通过尾部腹外侧延髓控制血压

• 批准号: 7899439
• 负责人: ANN M SCHREIHOFER
• 金额: $ 35.72万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7899439
• 关键词: Acute; Affect; Baroreflex; Brain; Breathing; Cardiovascular Diseases; Cardiovascular system; Cell Nucleus; Chemoreceptors; Chronic; Complex; Coupling; Essential Hypertension; Etiology; Exposure to; Figs - dietary; Glutamates; Goals; Health; Heart; Hypertension; Hypoxia; Individual; Lead; Link; Mediating; Modeling; Morbidity - disease rate; Nerve; Neurons; Nucleus solitarius; Obstructive Sleep Apnea; Patients; Pattern; Peripheral; Phase; Pressoreceptors; Rattus; Regulation; Research; Respiration; Risk; Role; Site; Sleep Apnea Syndromes; Source; Substance P Receptor; Testing; base; blood pressure regulation; depressed; expiration; mortality; neural circuit; novel; pressure; public health relevance; research study; respiratory; response

Essential hypertension is a leading form of cardiovascular disease that greatly increases the risks of morbidity and mortality. Many forms of essential hypertension are associated with augmented sympathetic nerve activity (SNA), although the basis of the sympatho-activation is not well understood. Obstructive sleep apnea is present in 30-50% of patients with essential hypertension, and the majority of patients with obstructive sleep apnea develop elevated SNA and arterial pressure (AP). Sleep apnea, characterized by chronic intermittent hypoxia, also alters central respiratory drive and the respiratory-related regulation of SNA. Cardio- respiratory integration appears to be at the heart of deficits observed with sleep apnea, because the elevated SNA and AP with sleep apnea are partially alleviated by altering nighttime breathing. Unfortunately, there is a paucity of information regarding the link between central respiratory drive and the elevated SNA that occurs with chronic intermittent hypoxia. The long range goals of this research are to elucidate central neural circuits that regulate the SNA that maintains AP and pinpoint alterations that may lead to elevated SNA and AP. This SNA is driven by neurons in the rostral ventrolateral medulla (RVLM), and the RVLM is powerfully restrained by GABAergic neurons in the caudal ventrolateral medulla (CVLM). The role of GABAergic CVLM neurons in the baroreflex control of SNA is established, but baro-activated GABAergic CVLM neurons also tonically inhibit the RVLM independent of baroreceptor inputs. In the previous period of this project we showed that central respiratory neurons provide multiple inputs to baro-activated GABAergic CVLM neurons in rats, although the sources are unknown. We also showed the CVLM is essential for evoking respiratory-related sympathetic responses to acute activation of peripheral chemoreceptors by hypoxia. These observations suggest that the CVLM is an important site for cardio-respiratory integration. The SNA that regulates AP is influenced by central respiratory neurons, but mechanisms underlying cardio-respiratory integration in the CNS are not understood. In Aims 1 and 2 of this renewal we will perform electrophysiological experiments in anesthetized rats to determine whether two central respiratory nuclei that project to the CVLM, the Kolliker-Fuse and pre- Botzinger nuclei, influence the activity of baro-activated CVLM neurons, and whether these inputs are selective for particular CVLM neurons or phases of the respiratory cycle. In addition, we will determine whether these inputs impact hypoxia-induced changes in CVLM neuronal activity and SNA. In Aims 3 and 4 we will determine whether regulation of the CVLM is altered by chronic intermittent hypoxia, as a model for obstructive sleep apnea. These studies will provide novel information regarding a powerful baroreceptor-independent influence upon the CVLM neurons that are likely to influence the RVLM, SNA, and AP. In addition, these studies will further our understanding of the impact of cardio-respiratory integration upon the regulation of blood pressure in health and hypertension.

原发性高血压是心血管疾病的一种主要形式，它大大增加了 发病率和死亡率。许多形式的原发性高血压与交感神经增强有关 神经活动（SNA），虽然交感神经激活的基础还没有很好地理解。阻塞性睡眠 30-50%的原发性高血压患者存在呼吸暂停，大多数阻塞性高血压患者存在呼吸暂停。 睡眠呼吸暂停会导致SNA和动脉压（AP）升高。睡眠呼吸暂停综合征的特征是慢性的 间歇性缺氧也改变了中枢呼吸驱动和SNA的呼吸相关调节。心脏- 呼吸整合似乎是睡眠呼吸暂停所观察到的缺陷的核心， SNA和AP伴睡眠呼吸暂停可通过改变夜间呼吸而部分缓解。不幸的是， 缺乏关于中枢呼吸驱动和SNA升高之间联系的信息， 慢性间歇性缺氧这项研究的长期目标是阐明中枢神经回路 调节维持AP的SNA，并查明可能导致SNA和AP升高的改变。这 SNA由延髓头端腹外侧区（RVLM）的神经元驱动，RVLM受到强烈的抑制 通过尾侧延髓腹外侧区（CVLM）的GABA能神经元。GABA能CVLM神经元在脑缺血再灌注中的作用 SNA的压力反射控制建立，但压力激活的GABA能CVLM神经元也紧张性抑制 RVLM不依赖于压力感受器输入。在这个项目的前一阶段，我们表明，中央 呼吸神经元提供多种输入的压力激活GABA能CVLM神经元在大鼠，虽然， 来源不明。我们还表明，CVLM是必不可少的，为唤起与麻醉相关的交感神经， 对缺氧引起的外周化学感受器急性激活的反应。这些观察表明， CVLM是心肺整合的重要部位。调节AP的SNA受到以下因素的影响： 中枢呼吸神经元，但中枢神经系统中的心肺整合机制不是 明白在本次更新的目标1和目标2中，我们将在麻醉状态下进行电生理实验。 大鼠，以确定是否有两个中央呼吸核投射到CVLM，Kolliker-Ehrman和前， Botzinger核影响压力激活的CVLM神经元的活动，以及这些输入是否是选择性的。 对于特定的CVLM神经元或呼吸周期的阶段。此外，我们将确定这些 输入影响低氧诱导的CVLM神经元活性和SNA的变化。在目标3和4中，我们将 确定慢性间歇性缺氧是否改变了CVLM的调节，作为阻塞性肺疾病的模型。 睡眠呼吸暂停这些研究将提供新的信息，关于一个强大的压力感受器独立 对CVLM神经元的影响可能影响RVLM、SNA和AP。另外这些 研究将进一步加深我们对心肺整合对调节 健康血压和高血压。