BRAIN MICROCIRCULATION AND ENDOTHELIAL INJURY

我们的长期目标是扩大我们对机制的了解 调节脑部微循环。这些机制至关重要。 在为大脑提供适当的流量方面，大脑的功能尤其是 对氧气和营养物质的输送受损敏感。目前的研究 关注内皮在控制小动脉直径中的作用，以及 关于内皮损伤可以扰乱血流的方式。两组 研究已经计划好了。它们都是相对独特的，因为它们都是 对体内微循环的影响。小鼠大脑表面的小动脉是 通过活体显微镜观察。第一组研究调查了 内皮细胞在产生舒缩因子中的作用 (EDRF，EDCFs)在被选择性血管活性激动剂刺激时或在 自动调节使血压升高。内皮损伤， He-Ne激光/伊文斯蓝原位产生焦点丢失 生产EDRF或EDCFs的能力，并提供一种用于测试 激动剂的作用依赖于这样的内皮机制。 药理探针，然后进行化学测量，将用于 确定内皮衍生介质的化学性质(例如 前列腺素、其他二十烷类化合物)。我们还将使用药理探针来 确定蛋白激酶C以及鸟苷酸盐或腺苷酸盐的作用 环化酶和L-精氨酸在调节血管紧张素转换酶合成、释放或作用中的作用 内皮细胞衍生的介质。第二组研究涉及 血管内皮细胞损伤对血小板聚集的影响 小动脉。药理探针将被用于研究改变的作用 抗聚集性内皮源性松弛因子的合成/释放 在促进局部血小板黏附/聚集中的作用 光/染料。在这样的部位捕获栓塞的血小板将是 短暂性脑缺血反复症状与其相关性的研究 袭击。药理探针将用于评估增加的作用 这种EDRF的释放在减少血小板聚集时的流动和 剪切力增大。L-精氨酸在调节血管紧张素转换酶中的作用 这种EDRF的抗聚集和抗粘连性能将是 调查过了。

Our long term goals are to expand our knowledge concerning mechanisms regulating brain microcirculation. These mechanisms are vitally important in providing appropriate flow to the brain, whose function is especially sensitive to impaired delivery of oxygen and nutrients. Present studies focus on the role of endothelium in controlling diameter of arterioles, and on the ways in which endothelial damage can derange flow. Two groups of studies are planned. All are relatively unique because they are conducted on microcirculation in vivo. Surface arterioles on the mouse brain are observed by intravital microscopy. The first group of studies investigates the role of endothelium in producing relaxing or constricting factors (EDRFs, EDCFs) when stimulated by selective vasoactive agonists or during autoregulation to an increase in blood pressure. Endothelial injury, produced in situ by helium neon laser/Evans blue causes a focus of lost capacity to produce EDRFs or EDCFs and provides a method for testing which agonists are dependent upon such an endothelial mechanism for their action. Pharmacologic probes, followed by chemical measurements will be used to determine the chemical nature of the endothelium derived mediators (e.g. prostanoids, other eicosanoids). We will also use pharmacologic probes to determine the role of protein kinase C, and of guanylate or adenylate cyclase and of L-arginine in mediating the synthesis, release or effects of the endothelium derived mediators. The second group of studies concerns the production of platelet aggregation by endothelial injury in the arterioles. Pharmacologic probes will be used to study the role of altered synthesis/release of an antiaggregant endothelium derived relaxing factor in promoting local platelet adhesion/aggregation at a site injured by light/dye. The capture of embolizing platelets at such a site will be studied for its relevance to repetitive symptoms of transient ischemic attacks. Pharmacologic probes will be used to assess the role of increased release of such an EDRF in decreasing platelet aggregation when flow and shear are increased. The role of L-arginine in regulating the antiaggregating and antiadhesive properties of this EDRF will be investigated.