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: 6506517
• 负责人: VIRGINIA L. BROOKS
• 金额: $ 36.47万
• 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/6506517
• 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）：尽管在疾病状态（例如高血压和充血性心力衰竭）中明确的临床相关性，但交感神经系统的活性可以长期升高的机制尚不完全理解。 当前的假设在产生交感神经语调中唤起了体液因素的重要作用，例如血管紧张素II（ANGII）和渗透压（OSM）。 但是，尚未确定ANG II和OSM作用和相互作用以增加交感语调的机制和位点。 鼻腹外侧髓质（RVLM）是一个大脑区域，其中包含概念驱动交感神经前神经元的细胞，并且这些细胞的活性可能受ANGII和OSM的影响。 此外，水剥夺是一种状态，其特征是Angii和OSM的增加。 因此，该提案检验了以下假设：在水剥夺大鼠中，增加的Angii和OSM相互作用以通过包括RVLM中的作用的机制增强交感活性的滋补水平。 该假设将通过确定Angii AT1封锁的作用，并降低OSM对有意识的水剥夺大鼠的传递性交感神经活动的影响，部分进行检验。 其他实验将通过利用氨基甲酸酯麻醉的大鼠对Angii和Angii拮抗剂的显微注射以及其他主要的神经递质激动剂和拮抗剂来特异性地检查RVLM的作用。