SUBSTANCE P: A NEUROMEDIATOR AFFECTING CARDIAC FUNCTION

拟议的研究是基于P物质的假设 (SP)从心脏的感觉神经末梢释放， 发挥在正常监管中非常重要的局部效应 心功能和/或心脏病理生理学。 对这一假说的概念支持来自对SP的研究 参与对呼吸道的调节，在有强烈 大鼠局部感觉神经末梢释放P物质的证据 对呼吸道刺激物和随后的SP介导的呼吸道的反应 宫缩和水肿症。含有SP的神经纤维位于 心脏中的几个部位，以及SP样免疫反应可以 从这些纤维中释放出来。外源性SP已被证明 影响心脏功能的各个方面，包括冠状动脉 血液流动，但文献中有一些不一致之处 需要解决的问题。更直接地研究 内源性SP也是必需的。拟议的研究将针对 后两点。在第一系列拟议的实验中， SP对豚鼠离体液灌流的药理作用 心脏将会被检查。SP对灌流压的影响 将测量脑室张力和心室率。自.以来 心脏将以恒定的速度灌流，灌流压力将 与冠脉阻力成正比。特价 我们将注意血管的可能作用 血管内皮细胞在冠脉血管对SP和 组胺和自主神经介质在脑缺血再灌注损伤中的作用 P物质的心脏作用。在研究的第二阶段， 将进行实验以确定SP是否是 有助于低氧和低氧引起的冠状动脉血管扩张 冠状动脉闭塞。最初，低氧和冠状动脉的影响 将确定SP释放时的堵塞情况。接下来，回应 冠脉血管对缺氧和冠脉闭塞的影响 用辣椒素耗尽SP的心脏进行检查 前处理。拟议的实验将有助于 确定神经肽在疾病中的重要性的长期目标 心脏生理学和病理生理学。

The proposed study is based on the hypothesis that substance P (SP) is released from sensory nerve terminals in the heart and exerts local effects which are important in the normal regulation of cardiac function and/or in cardiac pathophysiology. Conceptual support for this hypothesis comes from studies of SP involvement in regulation of the airways where there is strong evidence for release of SP from local sensory nerve terminals in response to airways irritants and subsequent SP-mediated airway constriction and edema. SP-containing nerve fibers are found at several sites in the heart, and SP-like immunoreactivity can be released from these fibers. Exogenous SP has been shown to affect various aspects of cardiac function, including coronary blood flow, but there are some inconsistencies in the literature which need to be resolved. More direct study of the function of endogenous SP is also needed. The proposed study will address the latter two points. In the first series of proposed experiments, the pharmacological actions of SP on the isolated, perfused guinea-pig heart will be examined. Effects of SP on perfusion pressure, ventricular tension and ventricular rate will be measured. Since hearts will be perfused at a constant rate, perfusion pressure will be directly proportional to coronary vascular resistance. Special attention will be given to the possible role of vascular endothelium in the response of the coronary vasculature to SP and the involvement of histamine and autonomic mediators in the cardiac actions of SP. In the second phase of the study, experiments will be done to determine if SP is a mediator which contributes to the coronary vasodilation produced by hypoxia and coronary occlusion. Initially, the effect of hypoxia and coronary occlusion on release of SP will be determined. Next, the response of the coronary vasculature to hypoxia and coronary occlusion will be examined in hearts which have had SP depleted by capsaicin pretreatment. The proposed experiments would contribute to the long-term goal of determining the importance of neuropeptides in cardiac physiology and pathophysiology.