Vestibular Influences on the Sympathetic Nervous System

前庭对交感神经系统的影响

• 批准号: 7564734
• 负责人: BILL J YATES
• 金额: $ 32.04万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7564734
• 关键词: Animal Model; Animals; Attenuated; Bilateral; Blood; Blood Pressure; Blood flow; Brain Stem; Cardiovascular system; Cells; Chest; Conscious; Drops; Excision; Fast Blue; Felis catus; Femoral vein; Force of Gravity; Forelimb; Funding; Gastrointestinal tract structure; Grant; Head; Heart; Hindlimb; Histocompatibility Testing; Inferior vena cava structure; Injection of therapeutic agent; Label; Lesion; Limb structure; Location; Mediating; Methods; Motor; Movement; Muscle; Neural Pathways; Neuraxis; Neurons; Orthostatic Hypotension; Pathway interactions; Patients; Pattern; Perfusion; Peripheral; Population; Positioning Attribute; Posture; Predisposition; Pressoreceptors; Research; Rhizotomy procedure; Role; Rotation; Signal Transduction; Skeletal Muscle; Spinal; Spinal Cord; Suid Herpesvirus 1; Sympathetic Nervous System; Syncope; System; Testing; Therapeutic; Time; Tissues; Tracer; Vascular resistance; Vasomotor; Venous; Ventral Roots; body position; common iliac vein; diamidino yellow; human subject; insight; labyrinthectomy; nerve supply; neurophysiology; peripheral blood; prevent; public health relevance; research study; response

DESCRIPTION (provided by applicant): Over the past 20 years, research on animal models as well as human subjects has demonstrated that the vestibular system contributes to regulating the distribution of blood in the body through effects on the sympathetic nervous system. Elimination of vestibular inputs attenuates the increase in vascular resistance that ordinarily occurs in the lower body during head-up tilts, resulting in increased blood flow to the hindlimbs. Presumably, this increased perfusion of the hindlimbs during head-up rotations produces peripheral blood pooling and a decrease in venous return to the heart, although this hypothesis has not been verified experimentally. Specific Aim 1 will determine whether removal of labyrinthine signals provides for a reduction in venous blood flow from the lower body during head-up body alterations, which would increase susceptibility for orthostatic hypotension. Head-up rotations additionally result in an increase in vascular resistance in the forelimb, although a bilateral vestibular neurectomy does not attenuate this response, as occurred in the hindlimb. This result indicates the existence of neural pathways that independently control sympathetic outflow to the forelimb and hindlimb. Specific Aim 2 will employ neuroanatomical methods to ascertain whether separate populations of neurons in the principal vasomotor region of the brainstem, the rostral ventrolateral medulla (RVLM), regulate sympathetic outflow to the upper and lower body. Additionally, Specific Aim 2 will utilize neurophysiological recordings to determine whether RVLM neurons regulating sympathetic outflow to the upper and lower body respond differently to vestibular stimulation. Although removal of vestibular inputs through a bilateral vestibular neurectomy attenuates cardiovascular adjustments during head-up postural alterations, the ability to rapidly adjust blood pressure and blood flow during such movements returns over time. Recent findings suggest that baroreceptor and vestibular inputs adjust sympathetic outflow during movement in an additive fashion. In addition, RVLM neurons receive convergent vestibular and baroreceptor inputs and provide the major pathway relaying both signals to sympathetic preganglionic neurons. Thus, increases in the response gain of RVLM neurons to baroreceptor inputs following the elimination of labyrinthine signals could offset the loss of vestibulo-sympathetic responses. Specific Aim 3 will establish whether responses of RVLM neurons to head-up tilts are attenuated following a bilateral labyrinthectomy, but recover in parallel with enhanced responses of the cells to baroreceptor inputs. These experiments will contribute to understanding the mechanisms through which cardiovascular adjustments are made during movement and changes in posture, and may provide insights towards developing therapeutic approaches to alleviate autonomic disturbances in patients with central or peripheral vestibular lesions. PUBLIC HEALTH RELEVANCE Standing from a lying or sitting position produces considerable challenges to the cardiovascular system, as gravity causes blood to shift from the thorax to the extremities, resulting in a decrease in the return of blood to the heart. This condition, called orthostatic intolerance, can bring about fainting if not corrected quickly. The proposed research considers the role of the vestibular system in compensating for orthostatic hypotension.

描述（由申请人提供）：在过去的20年中，对动物模型以及人类受试者的研究已经证明，前庭系统通过对交感神经系统的影响来调节体内血液的分布。前庭输入的消除减弱了血管阻力的增加，血管阻力的增加通常发生在头向上倾斜时的下半身，导致增加的血液流向后肢。据推测，这种增加灌注的后肢在头向上旋转产生外周血池和静脉回流到心脏的减少，虽然这一假设尚未得到实验验证。具体目标1将确定在头高位身体改变期间，去除精氨酸信号是否会减少来自下体的静脉血流量，这将增加直立性低血压的易感性。头向上旋转还导致前肢血管阻力增加，尽管双侧前庭神经切除术不会减弱这种反应，如后肢。这一结果表明存在独立控制交感神经流出前肢和后肢的神经通路。具体目标2将采用神经解剖学方法，以确定是否在脑干的主要血管区，延髓头端腹外侧（RVLM），调节交感神经流出到上半身和下半身的单独的神经元群体。此外，特定目标2将利用神经生理学记录来确定调节交感神经流出到上半身和下半身的RVLM神经元是否对前庭刺激有不同的反应。虽然通过双侧前庭神经切除术去除前庭输入减弱了头向上姿势改变期间的心血管调节，但在这种运动期间快速调节血压和血流的能力随着时间的推移而恢复。最近的研究结果表明，压力感受器和前庭输入调节交感神经在运动过程中的输出在一个加性的方式。此外，RVLM神经元接受会聚性前庭和压力感受器输入，并提供将这两种信号中继到交感节前神经元的主要通路。因此，在RVLM神经元的压力感受器输入的反应增益的增加，消除后的肾上腺素信号可以抵消前庭交感神经反应的损失。具体目标3将建立是否RVLM神经元的反应，头向上倾斜后，双边histothecomy衰减，但恢复与增强反应的细胞压力感受器输入平行。这些实验将有助于了解心血管调整的机制，通过在运动和姿势的变化，并可能提供见解发展的治疗方法，以减轻自主神经紊乱的患者中枢或外周前庭病变。与公共卫生的相关性从卧位或坐姿站立会对心血管系统产生相当大的挑战，因为重力会导致血液从胸腔转移到四肢，导致血液回流到心脏的减少。这种情况称为直立不耐受，如果不迅速纠正，可能导致昏厥。这项研究考虑了前庭系统在补偿体位性低血压中的作用。