Sympathetic Axonal Activity in Conscious Rats During Development of Hypertension

描述（由申请人提供）：交感神经活动（SNA）已在有意识的人类和动物中记录了30多年，目的是确定SNA升高是否有助于心脏病和高血压的发展。虽然这一过程已经变得相对普遍，但（1）记录的持续时间和（2）对功能不同的神经元的多单位活动的解释仍然存在问题。我们的实验室和其他一些实验室现在已经在清醒的动物中进行了长期SNA记录（周），允许在心血管疾病的发展过程中检查SNA。第二个问题已经在清醒的人和麻醉的动物中分别使用经皮高阻抗电极和神经解剖来解决。不幸的是，这两种方法都不允许长期记录单个轴突。本建议旨在开发程序记录单个单位SNA在清醒的大鼠在发展过程中的高血压。我们已经能够在清醒的大鼠中记录肾神经、肾上腺神经和腰神经中的单个轴突超过两周。该提案将开发用于分离和表征单个轴突的技术，这些轴突可以长时间（几天到几周）记录。最后，这种方法将被用来直接检查活动的单一特征的交感神经元在DOCA/盐高血压的发展。我们将在单个轴突中确定盐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动有关。此外，我们将直接研究SNA升高是否是由于单个神经元更频繁地放电，或者在实验性高血压的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。本项目旨在开发一种方法，通过记录高血压发展过程中的单个交感神经直接验证这一假设。这一过程可能为证明交感神经系统在心血管疾病中的作用提供一种新的和直接的方法。

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.