Humoral Interactions in long-term blood pressure control

描述（由申请人提供）：尽管在高血压和充血性心力衰竭等疾病状态中具有明确的临床相关性，但交感神经系统活性长期升高的机制尚不完全清楚。目前有一种假说认为，诸如血管紧张素II （ANGII）和渗透压（OSM）等体液因子在交感神经张力的产生中起着重要作用。然而，angii和OSM作用和相互作用以增加交感神经张力的机制和部位尚未确定。延髓吻侧腹外侧区（RVLM）是一个包含细胞的脑区，该细胞的活动可能受到ANGII和OSM的影响，这些细胞的张力驱动交感神经节前神经元。此外，缺水是一种以ANGII和OSM增加为特征的状态。因此，本研究验证了在缺水大鼠中，增加的ANGII和OSM通过包括RVLM中的作用在内的机制相互作用以提高交感神经活动的紧张水平的假设。这一假设将通过确定ANGII AT1阻断和OSM减少对有意识缺水大鼠传出交感神经活动的影响来部分验证。其他实验将通过使用聚氨酯麻醉的大鼠显微注射ANGII和ANGII拮抗剂，以及其他主要的神经递质激动剂和拮抗剂，专门研究RVLM的作用。

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.