BRAIN MICROCIRCULATION AND ENDOTHELIAL INJURY

微血管损伤，没有内皮剥脱，是由 两种不同的技术(1)使用汞灯的光/染料技术 和血管内荧光素(2)He-Ne激光在存在的情况下 埃文是蓝色的。即使没有内皮剥离，内皮损伤 产生局部的血小板聚集并改变色调(直径) 损伤的微血管。内皮损伤也改变了正常 乙酰胆碱对收缩的扩张作用。后者表明 干扰内皮细胞依赖性松弛因子(EDRF)和 证明了大脑中可能存在这样的因素 微血管。刚才描述的影响是在软脑膜血管中监测的 使用活体显微镜观察小鼠。负责地方政府的机制 血小板聚集和改变的音调将使用 与下列物质相互作用的药理探针： 环氧合酶-前列腺素-血栓素途径，与前列环素，与 脂氧合酶，具有钙通道。我们将尝试模仿对 使用产生自由基或血栓素的试剂造成的伤害。我们也会 血管内皮依赖性舒张因子(S)在心脏血管内皮细胞的表达 微循环，与性质分析的因素(S)通过 药理探针的使用。最后，在我们的因素分析中 干扰内皮细胞损伤后的血小板聚集， 我们将分别研究体外的血小板聚集和血管壁 使用电子显微镜。后面的这些研究将开始确定 在体内影响血小板反应的药物是否真的 作用于血小板，或者它们是否在改变或同时改变 脉管壁的损伤程度。拟议的研究与以下方面有关 重要的临床问题，如(1)小脑梗塞 血管内皮损伤后血管阻塞(2)血管肥厚 小动脉壁可能依赖于平滑肌的释放 增强血小板聚集过程中的有丝分裂原(据报道，发生在 高血压)(3)内皮损伤后血管反应性改变 在各种情况下，如缺血，高血压，血管破裂 蛛网膜下腔出血，外伤。

Microvascular injury, without denudation of endothelium is produced with two different techniques (1) a light/dye technique employing a mercury lamp and intravascular sodium fluorescein (2) a He-Ne laser in the presence of Evan's blue. Even without endothelial denudation the endothelial injury produces local platelet aggregation and alters the tone (diameter) of the injured microvessels. The endothelial injury also changes the normal dilating action of acetylcholine to a constriction. The latter suggests interference with an endothelial dependent relaxing factor (EDRF) and demonstrates the probable existence of such a factor in brain microvessels. The effects just described are monitored in pial vessels of mice using intravital microscopy. The mechanisms responsible for the local platelet aggregation and the altered tone will be investigated using pharmacologic probes interacting with the following: cyclooxygenase-prostaglandin-thromboxane pathway, with prostacyclin, with lipoxygenase, with calcium channels. We will attempt to mimic responses to injury by using agents producing radicals or thromboxane. We also will couple the demonstration of endothelium dependent relaxing factor(s) in the microcirculation, with an analysis of the nature of the factor(s) through the use of pharmacologic probes. Finally, in our analysis of factors interferring with platelet aggregation in response to endothelial injury, we will separately study platelet aggregation in vitro, and vessel walls using electromicroscopy. These latter studies will begin to determine whether drugs that affect the response of platelets in vivo, are actually working on the platelet or whether they are, instead or also, altering the amount of injury at the vessel wall. The proposed studies are relevant to important clinical problems such as (1) cerebral infarction due to small vessel obstruction following endothelial damage (2) hypertrophy of arteriolar walls which might be dependent upon release of smooth muscle mitogens during enhanced platelet aggregation (reported by some to occur in hypertension) (3) altered vascular reactivity following endothelial injury in such diverse conditions as ischemia, hypertension, vascular rupture with subarachnoid hemorrhage, trauma.