CONTROL OF MICROCIRCULATORY EXCHANGE FUNCTION

我们将研究假设a）微循环交换 职能由一个制衡系统来调节，以及B） 激动剂和内皮细胞之间的生物化学和分子相互作用 起到控制微循环交换功能的作用。 这 假设将通过追求以下目标来实现：1） 确定和表征微分电阻和交换容器 对缓激肽（BK）、腺苷（ADO）和血小板活化的反应 血小板活化因子（PAF）; 2）确定白细胞粘附和 大分子运输的迁移;和3）确定生物化学 ADO、BK和PAF影响微循环交换的途径 功能 活体荧光显微镜，荧光分光光度法， 放射免疫分析和计算机辅助视频图像数字处理 方法将用于测量仓鼠中大分子的转运 颊囊微循环钙进入抑制剂（维拉帕米）和 蛋白激酶C（鞘氨醇）将被应用于深入了解 由激动剂之间的相互作用产生的分子事件， 内皮细胞 据认为，该项目的成果将提供一个重要的 理解微循环调节机制的关键 交易所 微循环病理生理学的知识是必不可少的 用于开发炎症和血管疾病的治疗。

We will investigate the hypothesis that a) microcirculatory exchange function is regulated by a system of checks and balances, and b) biochemical and molecular interactions between agonists and endothelium play a role in controlling microcirculatory exchange function. This hypothesis will be approached by pursuing the following aims: 1) to determine and characterize the differential resistance and exchange vessel responses to bradykinin (BK), adenosine (ADO) and platelet activating factor (PAF); 2) to determine the influence of leukocyte adhesion and migration on macromolecular transport; and 3) to determine the biochemical pathways by which ADO, BK and PAF influence microcirculatory exchange function. Intravital fluorescent videomicroscopy, spectrofluorometry, radioimmunoassay and computer assisted videoimage digital processing methods will be used to measure transport of macromolecules in the hamster cheek pouch microcirculation. Inhibitors of calcium entry (verapamil) and of protein kinase C (sphingosine) will be applied to gain insight into the molecular events produced by the interactions between agonists and endothelium. It is submitted that the results of this project will provide an important key to the understanding of the regulatory mechanisms of microcirculatory exchange. This knowledge of microcirculatory pathophysiology is essential for the development of therapy for inflammation and vascular diseases.