Humoral Interactions in long-term blood pressure control

长期血压控制中的体液相互作用

• 批准号: 6612925
• 负责人: VIRGINIA L. BROOKS
• 金额: $ 33.98万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-12 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612925
• 关键词: angiotensin II; blood pressure; body water dehydration; hypertension; laboratory rat; medulla oblongata; neuroregulation; osmotic pressure

DESCRIPTION (provided by applicant): Despite clear clinical relevance in disease states such as hypertension and congestive heart failure, the mechanisms by which activity of the sympathetic nervous system can be chronically elevated are incompletely understood. A current hypothesis invokes an important role for humoral factors, such as angiotensin II (ANGII) and osmolality (OSM) in the generation of sympathetic tone. However, the mechanisms and sites at which ANG II and OSM act and interact to increase sympathetic tone have not been identified. The rostral ventrolateral medulla (RVLM) is a brain region that contains cells that tonically drive sympathetic preganglionic neurons, and the activity of these cells may be influenced by ANGII and OSM. Moreover, water deprivation is a state characterized by increases in both ANGII and OSM. Therefore, this proposal tests the hypothesis that in water deprived rats, increased ANGII and OSM interact to enhance the tonic level of sympathetic activity by a mechanism that includes actions in the RVLM. This hypothesis will be tested in part by determining the effects of ANGII AT1 blockade and decreases in OSM on efferent sympathetic nerve activity in conscious water deprived rats. Additional experiments will specifically examine the role of the RVLM by utilizing urethane-anesthetized rats for microinjections of ANGII and ANGII antagonists, as well as other major neurotransmitter agonists and antagonists.

描述（由申请人提供）：尽管与高血压和充血性心力衰竭等疾病状态有明确的临床相关性，但交感神经系统活动长期升高的机制尚不完全清楚。 目前的假设认为体液因素在交感神经张力的产生中发挥着重要作用，例如血管紧张素 II (ANGII) 和渗透压 (OSM)。 然而，ANG II 和 OSM 作用和相互作用以增加交感张力的机制和位点尚未确定。 延髓头端腹外侧区 (RVLM) 是一个大脑区域，包含强直性驱动交感神经节前神经元的细胞，这些细胞的活动可能受到 ANGII 和 OSM 的影响。 此外，缺水是一种以 ANGII 和 OSM 增加为特征的状态。 因此，该提议测试了这样的假设：在缺水的大鼠中，增加的 ANGII 和 OSM 相互作用，通过包括 RVLM 中的作用的机制来增强交感神经活动的强直水平。 这一假设将通过确定 ANGII AT1 阻断和 OSM 减少对清醒缺水大鼠传出交感神经活动的影响来部分检验。 其他实验将通过利用聚氨酯麻醉的大鼠显微注射 ANGII 和 ANGII 拮抗剂以及其他主要神经递质激动剂和拮抗剂来专门检查 RVLM 的作用。