Sympathetic Axonal Activity in Conscious Rats During Development of Hypertension

描述(申请人提供)：30多年来，在有意识的人类和动物中记录了交感神经活动(SNA)，目的是确定SNA升高是否有助于心脏病和高血压的发展。尽管这一过程已经变得相对常见，(1)记录的持续时间和(2)对功能不同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几个实验室现在已经在清醒的动物身上进行了长期的SNA记录(几周)，以便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类和麻醉的动物中分别使用经皮高阻抗电极和神经解剖得到解决。不幸的是，这两种方法都不允许长期记录单个轴突。这项建议旨在开发在高血压发展过程中记录清醒大鼠的单单位SNA的程序。我们已经能够在清醒大鼠的肾、肾上腺和腰部神经中记录超过两周的单个轴突。这项提议将开发分离和表征可长时间(几天到几周)记录的单个轴突的技术。最后，这一方法将被用来直接检测DOCA/盐性高血压发展过程中单个特征交感神经元的活动。我们将在单个轴突中确定盐皮质激素性高血压的早期阶段是否与更多的静息或诱发交感神经活动有关。此外，我们将直接检查SNA升高是由于个别神经元更频繁地放电，还是由于在实验性高血压的发展过程中招募了更多的神经元。与公共健康相关：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。这个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来直接检验这一假说。这一过程为证明交感神经系统在心血管疾病中的作用提供了一种新的直接方法。

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.