OXIDANTS AND NITRIC OXIDE IN CORONARY VASCULAR FUNCTION

本项目的长期目标是了解 氧化剂和一氧化氮的作用和作用机制 冠状循环中血管功能的相互作用， 确定在心力衰竭的这些过程中发生的改变， 和运动训练模式中检查的程序项目。 第一 目标是确定控制生产的机制， 超氧阴离子（O（2））的代谢及其与 内皮源性一氧化氮（NO），可能与 （1）正常冠状动脉循环和（2） 来自项目内合作的组织改变 心力衰竭和运动训练项目。 第二个目标是 以确定如何参与控制冠状动脉的信号机制， 正常动脉中的血管张力被O（2）-NO相互作用改变， 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导致 控制力生成的机制。 第三个目标是 阐明控制心脏（和 骨骼肌）组织呼吸内皮源性NO，与 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， 心力衰竭和运动训练模型的结果。 研究的 研究新信号机制的项目将在隔离的 小牛冠状动脉、微血管和心肌切片。 的 合作研究的重点是检查信号的变化， 将对以下动物进行机制研究：孤立的正常和衰竭犬冠状动脉 动脉、微血管和心脏及骨骼肌切片，并分离 正常和运动的大鼠主动脉和骨骼肌切片，并分离 正常和衰竭的人类心肌 关于变革的合作研究 NO合成酶和SOD酶的活性、酶水平和mRNA水平 还将用于确定故障变化的根源 和运动训练模型。 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 冠状动脉循环功能的相互作用，以及 确定在作用和作用机制方面发生的变化， 心力衰竭和运动中这些与血管功能相关的过程 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.