OXIDANTS AND NITRIC OXIDE IN CORONARY VASCULAR FUNCTION

这个项目的长期目标是加深对 氧化剂和一氧化氮的作用及其机制 冠脉循环中血管功能的相互作用 确定心力衰竭在这些过程中发生的变化 以及在计划项目中考察的运动训练模式。第一 目标是确定控制生产和生产的机制 超氧阴离子(O(2))的代谢及其与氧的相互作用 血管内皮细胞衍生的一氧化氮(NO)可能与 (1)正常冠脉循环和(2)的信号功能 计划内合作产生的组织变化 关于心力衰竭和运动训练的项目。第二个目标是 以确定信号机制如何参与控制冠状动脉 O(2)-NO相互作用改变正常动脉的血管张力 血管组织中这种相互作用的变化是如何从 心力衰竭和运动训练的动物会导致心脏的改变 控制力量产生的机制。第三个目标是 阐明心脏(和心脏)控制的机制(S) 骨骼肌)由内皮源性NO引起的组织呼吸 关注氧化剂相互作用在正常心肌中的作用 确定这些过程在组织中的功能变化 从心力衰竭和运动训练模式。在这方面的研究 研究新信令机制的项目将在孤立的 小腿冠状动脉、微血管和心肌切片。这个 协作研究的重点是检查信令的变化 机制将在：分离的正常和衰竭的犬冠状动脉上进行 动脉、微血管、心肌和骨骼肌切片和分离 正常和运动大鼠主动脉和骨骼肌切片，并分离 正常和衰竭的人类心肌。关于变化的协作研究 在一氧化氮合酶和超氧化物歧化酶活性、酶水平和mRNA 还将用于确定故障中更改的来源 和运动训练模式。这些研究的结果应该提供 对了解氧化剂和NO的作用有价值的信息 冠脉循环功能中的相互作用，以及 确定在作用和行动机制方面发生的变化 心力衰竭和运动中的这些血管功能相关过程 训练。

The long-range goals of this project are to develop an understanding of the roles and mechanisms of action of oxidant and nitric oxide interactions in vascular function in the coronary circulation and to identify alterations that occur in these processes in the heart failure and exercise training models examined in the Program Project. The first objective is to determine mechanisms that control the production and metabolism of superoxide anion (O(2)) and its interaction with endothelium-derived nitric oxide (NO) that are of potential relevance to signalling functions of (1) the normal coronary circulation and (2) alterations in tissues derived from collaborations within the Program Project on heart failure and exercise training. The second objective is to determine how signalling mechanisms involved in the control coronary vascular tone in normal arteries are altered by O(2))-NO interactions and how changes in this interaction in vascular tissue derived from during heart failure and exercise trained animals result in alterations in mechanisms that control force generation. The third objective is to elucidate the mechanism(s) involved in the control of cardiac (and skeletal muscle) tissue respiration by endothelium-derived NO, with a focus on the role of oxidant interactions in normal cardiac muscle and to identify changes in the function of these processes in tissues derived from the heart failure and exercise training models. Studies in this project examining new signalling mechanisms will be conducted in isolated calf coronary arteries, microvessels and cardiac muscle slices. The collaborative studies focused on examining changes in signalling mechanisms will be conducted on: isolated normal and failing dog coronary arteries, microvessels and cardiac and skeletal muscle slices and isolated normal and exercised rat aorta and skeletal muscle slices, and isolated normal and failing human heart muscle. Collaborative studies on changes in the activity, enzyme levels and mRNA of NO synthase and SOD enzymes will also be employed to identify the origins of changes in the failure and exercise training models. The results of these studies should provide valuable information for understanding the role of oxidant and NO interactions in the function of the coronary circulation, and in identifying changes that occur in the role and mechanism of action of these vascular function-related processes in heart failure and exercise training.