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: 10557788
• 负责人: Areum Kim Jensen
• 金额: $ 13.88万
• 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/10557788
• 关键词: Acceleration; 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; General Population; 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; Risk Reduction; 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; comparison control; effective therapy; exercise training; experience; experimental study; functional disability; improved; individuals with autism spectrum disorder; mortality; neural; neuromechanism; neuroregulation; peroneal nerve; pressure; prevent; response; restraint; 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.

项目总结