Metabolite effects on Group III and IV afferents

描述（由申请人提供）：对动态运动的心血管和呼吸反应已经确定，包括脉管系统交感放电增加，心率和收缩性增加，以及呼吸频率和潮气量增加。运动肌肉产生的反射被认为是造成这些效果的部分原因。本应用中提出的实验的总体目的是确定运动诱导的薄纤维肌肉传入神经（即III组和IV组）的机械和代谢刺激，这些刺激引起这些反射性自主神经和通气调节。通过对中脑运动区进行电刺激和可能的化学刺激，将在未麻醉的失脑猫中诱导动态运动。机械通道会被钆阻断。同样，代谢刺激将集中在花生四烯酸、缓激肽和嘌呤的环加氧酶产物上。吲哚美辛和类似的药物将被用来阻断环加氧酶的活性。HOE-140将用于阻断缓激肽-2受体，CGS-15943和PPADS将分别用于阻断Purinergic 1和2受体。这些“阻断剂”对动态运动中薄纤维传入放电的影响将在工作的三头肌表面肌肉自由灌注和其循环阻塞时进行检查。特别要注意的是运动后循环闭塞期，这是一种纯粹的代谢受体刺激。提出的研究应阐明机械和代谢刺激在刺激III组和IV组肌肉传入神经中所起的作用，从而引起运动压力反射。

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.