NEURAL AND HUMORAL MECHANISMS DURING HYPOVOLEMIA

低血容量期间的神经和体液机制

• 批准号: 3359025
• 负责人: TERRY N THRASHER
• 金额: $ 16.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3359025
• 关键词: afferent nerve; angiotensin II; baroreceptors; carotid sinus; denervation; dogs; experimental brain lesion; heart disorder; hemorrhage; hippocampus; hypovolemia; kidney disorder; renin angiotensin system; secretion; vasopressins; water drinking behavior

The objective of this application is to test the hypothesis that the renal renin-angiotensin system (Ang II) is as important as cardiac and arterial baroreceptor afferents in the stimulation of vasopressin (AVP) secretion and drinking in response to hypovolemia. The design of these studies employs comparisons of drinking and AVP responses induced by hypovolemia in conscious dogs, following selective removal of cardiac afferents, sinoaortic afferents or the subfornical organ (SFO). The techniques to be used include acute reversible blockade of cardiac nerves by intrapercardial infusion of procaine; chronic denervation of sinoaortic baroreceptors (SAD) or control of carotid sinus pressure following aortic baroreceptor denervation; and electrolytic ablation of the SFO which contains the central receptors activated by circulating Ang II to stimulate release of AVP and drinking in the dog. Hypovolemia will be induced by hemorrhage or acute reversible thoracic inferior vena caval constriction. The specific aims will test the hypothesis that cardiac afferents are not essential for stimulation of drinking and AVP release in response to hemorrhage. Preliminary results indicate that acute cardiac nerve blockade does not alter drinking and AVP release in response to hemorrhage, in contrast to recent studies, and indicate a prominent role for arterial and/or Ang II-dependent mechanisms. The hypothesis that Ang II and carotid sinus baroreceptors are important mechanisms will be tested by comparing responses following SAD and/or SFO ablation to control responses with and without acute cardiac nerve blockade. Carotid sinus pressure will be controlled in some studies to confirm results based on SAD. Finally, the hypothesis that pressor responses to Ang II in the euvolemic state inhibit drinking AVP secretions will be tested during control of carotid sinus pressure or acute cardiac nerve blockade. These studies evaluate basic mechanisms which control intake and retention of water via AVP and are essential to understanding derrangements in volume regulation in pathologic states involving the heart and kidneys.

该应用的目的是检验以下假设 肾素肾素 - 血管紧张素系统（ANG II）与心脏一样重要 和动脉压力受体传入刺激 加压素（AVP）分泌和饮酒 低血症。 这些研究的设计采用了 有意识中低血症引起的饮酒和AVP反应 狗在选择性去除心脏传入后，中质 传入或副脱机器官（SFO）。 这项技术是 使用的包括急性可逆封锁心脏神经 胸膜内注入Procaine；慢性改造 颈鼻窦压力的中级压力感受器（SAD）或控制 遵循主动脉压力感受器的神经神经支配；和电解 含有中央受体的SFO的消融 通过循环ANG II激活以刺激AVP的释放和 喝狗。 低血症将由出血诱导 或急性可逆的胸部下腔静脉收缩。 这 具体目的将检验以下假设：心脏传入是 对于刺激饮酒和AVP释放不是必不可少的 对出血的反应。 初步结果表明急性 心脏神经阻滞不会改变饮酒和AVP释放 与最近的研究相反，对出血的反应以及 表示动脉和/或ANG II依赖性的重要作用 机制。 Ang II和颈动脉窦的假设 压力感受器是重要的机制 将SAD和/或SFO消融后的响应与 控制反应有或没有急性心脏神经阻滞。 颈动脉窦压力将在某些研究中受到控制 基于SAD确认结果。 最后，假设 急诊室对euvoLemic状态中对ANG II的反应抑制饮酒 AVP分泌物将在控制颈动脉窦期间测试 压力或急性心脏神经阻滞。 这些研究评估 通过控制水的摄入和保留水的基本机制 AVP，对于理解数量的解答至关重要 涉及心脏和肾脏的病理状态的调节。