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

交感神经系统活动对自闭症谱系障碍患者血压调节的作用

• 批准号: 10333590
• 负责人: Areum Kim Jensen
• 金额: $ 14.04万
• 依托单位: SAN JOSE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333590
• 关键词: Acute; Adolescent and Young Adult; Attenuated; Autonomic Dysfunction; Baroreflex; Blood Pressure; Blood Vessels; Blood flow; Brain Stem; Buffers; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Chemicals; Child; Childhood; Chronic; Clinical Research; Contracts; Data; Development; Disease; Exercise; Exercise Test; Functional disorder; Future; Goals; Health; Heart Abnormalities; Heart Diseases; Heart Rate; High Prevalence; Hyperactivity; Hypertension; Impairment; Individual; Intervention; Ischemia; Measures; Mechanics; Mediating; Mentors; Muscle; Muscle Fibers; Neck; Nerve; Norepinephrine; Outcome; Patient Care; Periodicity; Plasma; Population; Quality of life; Reflex action; Rest; Risk; Role; Skeletal Muscle; Stroke; Structural defect; Sympathetic Nervous System; Techniques; Time; Vascular resistance; Vasoconstrictor Agents; autism spectrum disorder; autistic children; blood pressure control; blood pressure elevation; blood pressure reduction; blood pressure regulation; blood pressure variability; cardiovascular disorder risk; cardiovascular risk factor; clinical application; clinical efficacy; disorder control; effective therapy; exercise training; experience; experimental study; functional disability; improved; individuals with autism spectrum disorder; mortality; neuromechanism; neuroregulation; peroneal nerve; pressure; prevent; relating to nervous system; response; therapeutic target; therapeutically effective; vasoconstriction; young adult with autism spectrum disorder

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.

项目概要 该项目旨在阐明高血压和高血压患病率较高的病理生理学基础 自闭症谱系障碍 (ASD) 患者的心血管疾病。尽管有人建议 自闭症谱系障碍患者可能有交感神经过度活跃，使用间接措施的研究有限 执行。迄今为止，尚未对静息交感神经活动（SNA）进行直接测量 患有自闭症谱系障碍 (ASD) 的人。对剧烈运动的血压反应过度通常出现在个体中 与高血压和其他慢性疾病有关，血压的这种变化也与 未来中风和心血管死亡的风险增加。识别神经和血管机制 ASD 人群血压升高是为未来疗效研究提供信息的重要第一步 降低自闭症谱系障碍患者血压的临床干预措施；因此，它可以降低心血管死亡的风险。 运动期间引起的升压反应是神经输入的结果，包括激活 运动加压反射以引起交感神经兴奋和动脉压力反射的激活以引起交感神经 抑制。我们的目的是确定 SNA 升高是否是导致血压升高的主要原因 增强运动加压反射激活引起的 ASD 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导致运动期间血压升高 ASD（目标 2），以及动脉压力反射功能受损是否有助于增强 SNA 和血液 ASD 中的压力反应与对照组相比（目标 3）。在这些研究中，我们将直接测量肌肉 患有 ASD 的年轻人和健康人的 SNA、骨骼肌血流量和持续血压 休息时和运动时的控制。这项研究将是第一个调查神经控制的研究 使用最先进的技术研究 ASD 人群的心血管系统机制。迄今为止仅 已采用间接测量（例如静息心率和血压变异性）来了解 ASD 人群的自主神经功能障碍。我们将使用直接从腓神经测量肌肉 SNA 显微神经造影技术首次应用于自闭症谱系障碍人群的休息和运动过程中。识别 自闭症谱系障碍（ASD）中交感神经过度活跃很重要，因为它不仅会导致高血压，而且还可能 加速其他健康并发症的进展，包括心脏病，与血液升高无关 压力。此外，通过使用独特的无创变压颈室技术，我们将识别 不仅可以控制肌肉 SNA 的动脉压力感受反射，还可以控制静息时的血压 以及运动过程中。 总的来说，在具有自主神经临床应用专业知识的 SC2 导师的指导下 功能和运动测试以及健康和疾病训练，这项研究将开始确定病理生理学 ASD 患者的早期高血压和心血管疾病。研究结果将构成以下基础： 未来的实验和临床研究以确定有效的治疗目标，使患者病情得到改善 护理，并最终提高自闭症谱系障碍患者的生活质量。