EDRF & CARDIOVASCULAR CONTROL IN EXERCISE

描述：（改编自申请人摘要） 许多导致心脏变化的机制， 运动时输出量和外周血管阻力的变化及其作用 这些机制在长期运动训练后， 阐明。然而，最近人们认识到， 血流速度，可能通过剪切速率（或应力）的变化， 其本身导致大动脉血管舒张， 通过内皮细胞-EDRF依赖性机制抑制血管阻力。 由于运动是一种以血流量大幅增加为特征的状态 在冠状动脉和骨骼肌循环中，研究人员 假设急性运动刺激EDRF依赖性扩张， 大血管和小血管以及长期运动 条件反射，即。有氧训练，增强EDRF的释放，甚至 进一步。这种增强的释放最有可能是由于增加 由组成性酶产生EDRF，并可能负责 运动对人类疾病的有益心血管影响 states. 调查人员的初步数据表明， 通过以下方法消除运动期间体内的大冠状动脉直径 硝基-L-精氨酸，精氨酸代谢抑制剂。 的增加 运动时的体循环动脉压在阻断后甚至更大 EDRF合成 慢性运动调节（2小时7英里 每小时10天）增强大冠状动脉扩张， 乙酰胆碱在清醒的狗通过EDRF依赖机制。 在 离体、大心外膜和离体犬冠状动脉微血管 在长期运动后，亚硝酸盐的释放增加， 在基础状态和刺激后，NO的水合产物 乙酰胆碱。 新鲜采集的主动脉的北方印迹分析 来自这些狗的内皮细胞表明存在组成性的 EDRF合成酶。 研究人员的研究重点将是 确定：1）EDRF在急性心血管反应中的作用， 运动; 2）慢性运动调节后EDRF的作用; 3）如果 NO是这些效应的中介体;以及，4）是否有增强的 慢性运动后EDRF合成酶mRNA的产生 条件反射 慢性运动调节不仅增加血液 流向参与运动反应的器官， 降低全身性高血压，可能部分逆转心脏的影响， 疾病，并可能促进一般心血管健康。 研究人员的初步数据表明，EDRF直接参与了 在这项运动条件反射中，研究人员的研究将定义 在体内EDRF的作用，并将在体外确定的生化和 分子机制负责。

DESCRIPTION: (Adapted from the applicant's abstract) Many of the mechanisms which are responsible for changes in cardiac output and peripheral vascular resistance during exercise and the role of these mechanisms after chronic exercise training, have been elucidated. However, it has recently been recognized that increases in blood flow velocity, perhaps through changes in shear rate (or stress), in and of itself, result in vasodilation of both large arteries and resistance vessels through an endothelial cell-EDRF dependent mechanism. Since exercise is a state characterized by large increases in blood flow in the coronary and skeletal muscle circulations, the investigators have hypothesized that acute exercise stimulates EDRF dependent dilation of large and small blood vessels and furthermore that chronic exercise conditioning, ie. aerobic training, potentiates the release of EDRF even further.This enhanced release is most likely due to the increased production of EDRF by the constitutive enzyme and may be responsible for the beneficial cardiovascular effects of exercise in human disease states. The investigators preliminary data suggest that the increase in large coronary artery diameter in vivo during exercise is eliminated by nitro-L-arginine, an inhibitor of arginine metabolism. The increase in systemic arterial pressure during exercise is even larger after blockade of EDRF synthesis. Chronic exercise conditioning (2 hours at 7 miles per hour for 10 days) enhances the large coronary artery dilation to acetylcholine in conscious dogs through an EDRF dependent mechanism. In vitro, large epicardial and isolated coronary microvessels from the dogs after chronic exercise have an increased release of nitrite, the hydration product of NO, in the basal state and also after stimulation with acetylcholine. Northern blot analysis of freshly harvested aortic endothelial cells from these dogs indicates the presence of constitutive EDRF synthase. The focus of the investigators' studies will be to determine: 1) the role of EDRF in the acute cardiovascular response to exercise; 2) the role of EDRF after chronic exercise conditioning; 3) if NO is the mediator of these effects; and, 4) whether there is enhanced production of the mRNA for EDRF synthase after chronic exercise conditioning. Chronic exercise conditioning not only increases blood flow to the organs which participate in the exercise response but also reduces systemic hypertension, may partially reverse the effects of heart disease and may promote general cardiovascular well being.The investigators' preliminary data suggest that EDRF directly participates in this exercise conditioning, and the investigators' study will define in vivo the role of EDRF and will determine in vitro the biochemical and molecular mechanisms responsible.