Metabolite Effects on Group III and IV Afferents

代谢对第三组和第四组传入神经的影响

• 批准号: 8211002
• 负责人: Marc Peter Kaufman
• 金额: $ 38.39万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8211002
• 关键词: ASIC channel; Amiloride; Area; Attention; Attenuated; Blood Circulation; Bradykinin; Bradykinin Receptor; Breathing; Cardiac; Cardiovascular system; Cessation of life; Chemical Stimulation; Coronary Arteriosclerosis; Electric Stimulation; Exercise; Felis catus; Fiber; Frequencies; Heart; Hypothalamic structure; Lactic acid; Lead; Light; Limb structure; Mechanics; Metabolic; Midbrain structure; Muscle; Muscle Fibers; Patients; Peptides; Play; Purines; Reflex action; Reporting; Role; Running; Stimulus; Structure of popliteal artery; Suramin; Testing; Thick; Tidal Volume; Triceps Brachii Muscle; Walking; arm; heart rhythm; improved; prevent; public health relevance; purine; pyridoxal phosphate-6-azophenyl-2' ,4' -disulfonic acid; receptor; research study; response; spinal nerve posterior root

DESCRIPTION (provided by applicant): The cardiovascular and ventilatory responses to dynamic exercise are well known and include increases in sympathetic discharge to the vasculature, decreases in vagal discharge to the heart and airways as well as increases in tidal volume and breathing frequency. A reflex arising from the exercising muscles is believed to be mostly responsible for increases in sympathetic discharge to the vasculature, and probably contributes at least in part to the remaining effects. The overall aim of the proposed experiments is to determine the role played by mechanical and metabolic stimuli that arise in the dynamically exercising muscles in stimulating the thin fiber afferents (i.e., group III and IV) comprising the afferent arm of the reflex evoking these cardiovascular and ventilatory adjustments. Dynamic exercise will be induced in decerebrated unanesthetized cats by electrical and possibly chemical stimulation of the mesencephalic or subthalamic locomotor regions. [Three putative] metabolic stimuli will be investigated, namely lactic acid, ATP, a purine which stimulates P2 receptors, and bradykinin, a peptide that stimulates B2 receptors. The responses of group III and IV afferents to lactic acid will be blocked by both amiloride and A-317567, a compound reported to block acid sensing ion channels. Likewise, the responses of the afferents to ATP will be blocked by PPADS and suramin [and those to bradykinin will be blocked by HOE-140]. Each of the blocking agents will be injected into the popliteal artery perfusing the dynamically exercising triceps surae muscles. Afferent activity will be recorded from the L7-S1 dorsal roots both when the triceps surae muscles are freely perfused and when their circulation is occluded. Particular attention will be paid to a one minute period of post-exercise circulatory occlusion, which is a pure metabolic stimulus to group III and IV muscle afferents. The proposed studies should shed new light on the roles played by mechanical and metabolic stimuli in stimulating group III and IV muscle afferents during dynamic exercise. PUBLIC HEALTH RELEVANCE: We propose to determine the role played by mechanical and metabolic stimuli in evoking the cardiovascular and ventilatory responses to dynamic exercise (i.e., running). These responses are important because they support our ability to exercise in normal circumstances, but also can cause irregular heart rhythms, leading to death in patients with coronary artery disease. Increasing our understanding of the mechanisms causing these effects may lead to improved treatments for the cardiac problems occurring during exercise.

描述（由申请人提供）：对动态运动的心血管和通气反应是众所周知的，包括对脉管系统的交感神经排放，减少对心脏和气道的迷走式排放以及潮汐体积和呼吸频率的增加。据信，锻炼肌肉产生的反射主要是导致对脉管系统的同情排放的增加，并且可能至少部分造成了剩余影响。提出的实验的总体目的是确定机械和代谢刺激在刺激薄纤维传入（即III和IV组）中发挥的机械和代谢刺激的作用，这些刺激在刺激薄纤维传入（即III和IV组）中所起的作用，这些传入构成了这些心血管和频道调整的反射传入。通过对中脑或丘脑下运动区的电刺激或可能的化学刺激，将在未屈服的猫中诱导动态运动。 [三个推定]将研究代谢刺激，即乳酸，ATP，一种刺激P2受体的嘌呤和刺激B2受体的肽。 III和IV组传入对乳酸的反应将被Amiloride和A-317567封闭，A-317567是据报道阻断酸感应离子通道的化合物。同样，传入对ATP的反应将被PPADS和SURAMIN阻止（对Bradykinin的反应将被HOE-140阻止]。每种阻塞剂将被注入popliteal动脉中，以动态锻炼三头肌肌肉。当三头肌肌肉被自由灌注时，以及它们的循环被阻塞时，将从L7-S1背根记录传入活动。运动后循环闭塞一分钟，这是对III组和IV肌肉传入的纯粹代谢刺激。拟议的研究应新阐明机械和代谢刺激在动态运动过程中刺激III和IV肌肉传入中发挥的作用。 公共卫生相关性：我们建议确定机械和代谢刺激在唤起动态运动（即跑步）的心血管和通气反应中所起的作用。这些反应很重要，因为它们支持我们在正常情况下运动的能力，但也会引起不规则的心律，导致冠状动脉疾病患者死亡。提高我们对导致这些影响的机制的理解可能会改善运动过程中发生的心脏问题的治疗方法。