The Role of Sympathetic Nervous System Activity on Blood Pressure Regulation in Individuals with Autism Spectrum Disorder

项目总结 本项目旨在阐明高血压患病率较高的病理生理学基础和 孤独症谱系障碍(ASD)患者的心血管疾病。尽管有人建议， ASD患者可能有交感神经过度活动，使用间接测量方法的有限研究已经完成 已执行。到目前为止，还没有对静息交感神经活动(SNA)的直接测量 患有自闭症的个体。对急性运动的血压反应夸大通常见于个体。 患有高血压和其他慢性疾病，这种血压变化也与 增加未来中风和心血管死亡的风险。确定神经和血管机制 ASD人群中的血压升高是为未来的疗效研究提供必要的第一步 临床干预可以降低ASD患者的血压；因此，它可以降低心血管死亡的风险。 运动中诱发的升压反应是神经输入的结果，包括激活 运动加压反射引起交感神经兴奋，激活动脉压力感受器反射引起交感神经。 抑制力。我们的目标是确定SNA升高是否是导致血压升高的主要因素 运动加压反射激活引起的自闭症患者的运动(目标1)。此外，我们的目标是确定 交感神经介导的血管反应如何影响运动中的血压升高 ASD(目标2)，以及动脉压力感受性反射功能受损是否有助于SNA和血液的增加 ASD患者的压力反应与对照组的比较(目标3)。在这些研究中，我们将直接测量肌肉 青壮年ASD患者和健康人的SNA、骨骼肌血流量和持续血压 在休息和进行锻炼时进行控制。这项研究将是第一次研究神经控制。 用最先进的技术研究ASD人群的心血管系统机制。只是到目前为止 间接测量(例如，静息心率和血压变异性)已经被用来理解 自闭症患者的自主神经功能障碍。我们将直接测量来自腓神经的肌肉SNA 首次在ASD人群中进行静息和运动时的显微神经学检查。识别 交感神经过度活动在ASD中很重要，因为它不仅导致高血压，而且可能 加速包括心脏病在内的其他健康并发症的进展，而不依赖于血液的任何上升 压力。此外，通过使用独特的无创可变压力颈腔技术，我们将识别 不仅是肌肉SNA的动脉压力感受性反射控制，而且作为休息时的结果也控制了血压 以及在锻炼过程中。 总的来说，在拥有自主神经临床应用专业知识的SC2导师的指导下 在健康和疾病方面的机能和运动测试和训练，这项研究将开始确定病理生理学 ASD患者早期高血压和心血管疾病的风险。这些发现将构成以下方面的基础 未来的实验和临床研究，以确定有效的治疗目标，使患者得到改善 护理，并最终提高自闭症患者的生活质量。

PROJECT SUMMARY This project aims to elucidate the pathophysiological basis for the higher prevalence of hypertension and cardiovascular disease in individuals with Autism Spectrum Disorder (ASD). Although it has been suggested that individuals with ASD may have sympathetic hyperactivity, limited studies using indirect measures have been performed. To date, direct measures of resting sympathetic nerve activity (SNA) have not been made in individuals with ASD. An exaggerated blood pressure response to acute exercise is typically seen in individuals with hypertension and other chronic conditions, and such changes in blood pressure are also associated with an increased risk of future stroke and cardiovascular mortality. Identifying neural and vascular mechanisms of elevated blood pressure in the ASD population is an essential first step to inform future research on the efficacy of clinical intervention to lower blood pressure in ASD; thus, it could reduce the risk of cardiovascular mortality. The pressor response evoked during exercise is a result of neural inputs including activation of the exercise pressor reflex to cause sympatho-excitation and activation of arterial baroreflex to cause sympatho- inhibition. We aim to identify whether heightened SNA is a major contributor to augmented blood pressure during exercise in ASD caused by augmented exercise pressor reflex activation (Aim 1). Further, we aim to determine how sympathetically mediated vascular responses contribute to the blood pressure increase during exercise in ASD (Aim 2), and whether impaired arterial baroreflex function contributes to augmented SNA and blood pressure responses in ASD compared to controls (Aim 3). In these studies, we will directly measure muscle SNA, skeletal muscle blood flow, and continuous blood pressure in both young adults with ASD and healthy controls at rest and while they perform exercise. This study will be the first to investigate neural control mechanisms of the cardiovascular system in an ASD population using state-of-the-art techniques. Thus far only indirect measures (e.g., resting heart rate and blood pressure variability) have been employed to understand autonomic dysfunction in ASD population. We will measure muscle SNA directly from the peroneal nerve using microneurography technique for the first time in ASD population both at rest and during exercise. Identifying sympathetic overactivity in ASD is important because it not only contributes to the hypertension but also may accelerate the progression of other health complications including heart disease independent of any rise in blood pressure. In addition, by using the unique noninvasive variable pressure neck chamber technique, we will identify not only arterial baroreflex control of muscle SNA, but also control of blood pressure as an outcome both at rest and during exercise. Collectively, with guidance from SC2 mentors who have expertise in clinical applications of autonomic function and exercise testing and training in health and disease, this study will begin to identify pathophysiology of early hypertension and cardiovascular disease in individuals with ASD. The findings will form the basis for future experimental and clinical studies to determine an effective therapeutic target, enable improved patient care, and ultimately enhance the quality of life for individuals with ASD.