Sympathetic Axonal Activity in Conscious Rats During Development of Hypertension

高血压发展过程中清醒大鼠的交感神经轴突活动

• 批准号: 7664467
• 负责人: MARK M KNUEPFER
• 金额: $ 18.1万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7664467
• 关键词: Address; Adrenal Glands; Adrenergic Fibers; Animals; Arousal; Axon; Cardiovascular Diseases; Catecholamines; Characteristics; Conscious; Development; Dissection; Electrodes; Electroencephalography; Heart failure; Human; Hyperactive behavior; Hypertension; Individual; Kidney; Laboratories; Lumbar nerve; Methods; Modeling; Nerve; Neurons; Operative Surgical Procedures; Pattern; Phase; Plasma; Population; Procedures; Rat-1; Rattus; Recruitment Activity; Rest; Role; Stimulus; Sympathetic Nervous System; Techniques; Telemetry; Testing; design; heart rate variability; hypertensive heart disease; mineralocorticoid hypertension; novel; public health relevance; response; urinary

DESCRIPTION (provided by applicant): Sympathetic nerve activity (SNA) has been recorded in conscious humans and animals for more than 3 decades with the intent of determining whether elevated SNA contributes to the development of heart disease and hypertension. Although the procedure has become relatively common, (1) the duration of the recordings and (2) the interpretation of multiunit activity of functionally diverse neurons remain problematic. Our laboratory and a few others have now performed long term SNA recording (weeks) in conscious animals allowing the examination of SNA during the development of cardiovascular disease. The second problem has been addressed in conscious humans and anesthetized animals using percutaneous high impedence electrodes and nerve dissection, respectively. Unfortunately, neither approach allows for long term recording of individual axons. This proposal is designed to develop procedures for recording single unit SNA in conscious rats during the development of hypertension. We have been able to record from single axons in the renal, adrenal and lumbar nerves for more than two weeks in conscious rats. This proposal will develop techniques for isolating and characterizing single axons that can be recorded for prolonged periods (days to weeks). Finally, this approach will be used to directly examine the activity of single characterized sympathetic neurons during the development of DOCA/salt hypertension. We will determine in single axons whether the early phases of mineralocorticoid hypertension are associated with greater resting or evoked sympathetic nerve activity. Moreover, we will directly examine whether the elevated SNA is due to individual neurons firing more often or whether more neurons are recruited during the development of experimental hypertension. PUBLIC HEALTH RELEVANCE: Many studies have suggested that hypertension and heart disease may be caused by increased sympathetic nerve activity. This project is designed to develop a method for directly testing this hypothesis by recording from single sympathetic nerves during the development of hypertension. This procedure could provide a novel and direct method for proving the role of the sympathetic nervous system in cardiovascular disease.

描述（由申请人提供）：三十多年来在有意识的人和动物中记录了交感神经活动（SNA），目的是确定升高SNA是否有助于心脏病和高血压的发展。尽管该过程已经变得相对普遍，但（1）记录的持续时间以及（2）功能多样性神经元的多单位活动的解释仍然有问题。现在，我们的实验室和其他一些实验室在有意识的动物中进行了长期记录（数周），允许在心血管疾病发展过程中检查SNA。在有意识的人类和麻醉动物中分别使用经皮障碍物电极和神经解剖来解决了第二个问题。不幸的是，这两种方法都允许长期记录单个轴突。该建议旨在制定在高血压发展期间在有意识的大鼠中记录单个单位SNA的程序。我们能够从肾脏，肾上腺和腰椎神经中的单轴突中记录超过两周的意识大鼠。该提案将开发用于隔离和表征单轴的技术，这些技术可以长时间（天到几周）记录。最后，该方法将用于直接检查DOCA/盐高血压发展过程中单个特征性交感神经元的活性。我们将在单轴突中确定矿物皮质激素高血压的早期阶段是否与更大的静息或诱发的交感神经活性有关。此外，我们将直接检查升高的SNA是否是由于单个神经元发射的频率更高，还是在实验性高血压发展过程中是否招募了更多的神经元。公共卫生相关性：许多研究表明，高血压和心脏病可能是由交感神经活动增加引起的。该项目旨在开发一种通过在高血压发展过程中记录单个交感神经来直接检验该假设的方法。该程序可以提供一种新颖而直接的方法来证明交感神经系统在心血管疾病中的作用。