EDRF & CARDIOVASCULAR CONTROL IN EXERCISE

描述：(改编自申请人的摘要) 许多导致心脏疾病改变的机制 运动中输出量和外周血管阻力及其作用 在这些机制中，在慢性运动训练后， 已澄清。然而，最近人们认识到， 血流速度，可能是通过剪切率(或应力)的变化， 其本身导致大动脉和大动脉的血管扩张 阻力血管通过内皮细胞-EDRF依赖机制。 因为运动是一种以血液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依赖的血管扩张 大血管和小血管，此外，慢性运动 条件反射，即。有氧训练，甚至增强EDRF的释放 此外，这种增强的释放很可能是由于增加了 由构成酶产生EDRF，并可能负责 运动对人类疾病的有益心血管效应 各州。调查人员的初步数据表明， 通过以下方法消除运动时体内冠状动脉内径较大的情况 硝基-L-精氨酸，精氨酸代谢的抑制剂。这一增长 封堵后运动时的体动脉压更大 EDRF合成的关键技术。慢性运动调理(7英里2小时 每小时10天)增强大冠状动脉扩张至 清醒犬体内的乙酰胆碱通过EDRF依赖机制。在……里面 犬离体心外膜大血管和离体冠状微血管 在长期运动后，亚硝酸盐的释放增加， 基础状态和刺激后NO的水合产物 含有乙酰胆碱。新鲜主动脉的Northern印迹分析 这些狗的内皮细胞表明存在结构性 EDRF合成酶。调查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)慢性运动后EDRF的作用；3)如果 NO是这些影响的中介；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。慢性运动调理不仅增加血液 流向参与运动反应的器官，但也 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。 调查人员的初步数据表明，EDRF直接参与了 在这项练习中，研究人员的研究将确定 在体内EDRF的作用，并将在体外决定生化和 相关的分子机制。

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.