Metabolite effects on Group III and IV afferents

描述(申请人提供)：心血管和呼吸系统对动态运动的反应是明确的，包括交感神经对血管系统的放电增加，心率和收缩能力增加，以及呼吸频率和潮气量增加。锻炼肌肉产生的反射被认为是造成这些影响的部分原因。本申请中提出的实验的总体目标是确定运动诱导的对薄纤维肌肉传入(即组III和组IV)的机械和代谢刺激，从而引起这些反射、自主神经和呼吸调节。通过对中脑运动区的电刺激和可能的化学刺激，将在去大脑的未麻醉猫身上诱导动态运动。机械化的渠道将被Gd堵塞。同样，代谢刺激将集中在花生四烯酸、缓激肽和嘌呤的环氧合酶产物上。消炎痛和类似的作用剂将被用来阻断环氧合酶的活性。HOE-140将用于阻断缓激肽-2受体，CGS-15943和PPADS将分别用于阻断嘌呤能1和2受体。在动态运动中，当工作的小腿三头肌自由灌流和阻断循环时，将检验这些“阻滞剂”对细纤维传入放电的影响。运动后循环闭塞期将受到特别关注，这是一种纯粹的代谢型受体刺激。这项拟议的研究应该为机械和新陈代谢刺激在刺激III和IV组肌肉传入进而引发运动加压反射方面所起的作用提供新的线索。

DESCRIPTION (provided by applicant): The cardiovascular and respiratory responses to dynamic exercise are well established and include increases in sympathetic discharge to the vasculature, increases in heart rate and contractility, as well as increases in breathing frequency and tidal volume. A reflex arising from exercising muscles is believed to be partly responsible for these effects. The overall aim of the experiments proposed in this application is to determine the exercise-induced mechanical and metabolic stimuli to thin fiber muscle afferents (i.e., group III and IV) that evoke these reflex autonomic and ventilatory adjustments. Dynamic exercise will be induced in decerebrate unanesthetized cats by electrical and possibly chemical stimulation of the mesencephalic locomotor region. Mechanogated channels will be blocked by gadolinium. Likewise, metabolic stimuli will focus on cyclooxygenase products of arachidonic acid, bradykinin and the purines. Indomethacin and similar acting agents will be used to block cyclooxygenase activity. HOE-140 will be used to block bradykinin-2 receptors, and CGS-15943 and PPADS will be used to block Purinergic 1 and 2 receptors, respectively. The effects of these "blocking agents" on thin fiber afferent discharge during dynamic exercise will be examined both when the working triceps surae muscles are freely perfused and when their circulation is occluded. Particular attention will be paid to the period of post-exercise circulatory occlusion, which is a pure metaboreceptor stimulus. The proposed studies should shed new light on the roles played by mechanical and metabolic stimuli in stimulating the group III and IV muscle afferents that in turn evoked the exercise pressor reflex.