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.

项目摘要 该项目旨在阐明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。尽管有人认为， ASD患者可能有交感神经功能亢进，使用间接测量的有限研究已经被证实， 执行。到目前为止，还没有直接测量静息交感神经活动（SNA）， ASD患者。对剧烈运动的血压反应过度通常见于个体 与高血压和其他慢性疾病有关，血压的这种变化也与高血压和其他慢性疾病有关。 增加未来中风和心血管死亡的风险。识别神经和血管机制 ASD人群的血压升高是为未来的疗效研究提供信息的重要第一步。 临床干预以降低ASD患者的血压;因此，它可以降低心血管死亡率的风险。 在运动期间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，激活动脉压力反射引起交感神经兴奋， 抑制作用我们的目标是确定SNA升高是否是血压升高的主要因素， 运动引起的ASD增强运动升压反射激活（目的1）。此外，我们的目标是确定 交感神经介导的血管反应如何在运动中导致血压升高 ASD（目标2），以及受损的动脉压力反射功能是否有助于增强SNA和血液 ASD与对照组相比的压力反应（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、骨骼肌血流量和连续血压 控制在休息时，而他们进行锻炼。这项研究将是第一个调查神经控制 心血管系统的机制在ASD人群中使用国家的最先进的技术。到目前为止， 间接措施（例如，静息心率和血压变异性）已经被用来理解 ASD患者的自主神经功能障碍。我们将直接从腓神经测量肌肉SNA，使用 首次在ASD人群中进行静息和运动时的显微神经造影技术。识别 ASD中的交感神经过度活跃是重要的，因为它不仅有助于高血压，而且可能 加速其他健康并发症的进展，包括心脏病，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室技术，我们将识别 不仅动脉压力感受器反射控制肌肉SNA，而且控制血压作为结果， 和运动时。 在具有自主神经临床应用专业知识的SC2导师的指导下， 功能和运动测试和训练的健康和疾病，这项研究将开始，以确定病理生理学 ASD患者早期高血压和心血管疾病的风险这些发现将成为 未来的实验和临床研究，以确定有效的治疗目标，使改善患者 护理，并最终提高ASD患者的生活质量。