ERYTHROCYTE--A REGULATOR OF MICROVASCULAR PERFUSION

描述：(改编自调查人员摘要)这一目标 该项目是为了证实红细胞(RBC)在 外周微循环中微血管血流的调节。 氧气供应与需求的适当匹配需要一个传感器 组织需氧量和供氧量变化的效应器 这些需求。P.I.S早期的研究表明，红细胞氧气 含量比氧分压pO2更重要，对于 在严重缺氧条件下维持毛细血管供氧。因为唯一的 氧直接影响氧转运途径的一部分 含量是红细胞中的血红蛋白，有人建议红细胞必须 参与感知氧气需求和适当改变血液流量。 血管中红细胞含氧量在特定时间的水平 组织中的点直接与氧气的利用水平有关，通过 纸巾。如果移动的红细胞能够感知氧气需求并带来 关于血管口径的减少，这将提供一种有效的手段 随时随地增加血液流量和氧气输送 可能会出现。这将消除对多样化的传感网络的需求 血管系统的各个部位。由于ATP存在于红细胞中，这是 在低PO2和低pH时释放，当应用于铝内时 进入小动脉和小静脉会引发一种传导的血管扩张反应， 假设红细胞是组织需氧量的传感器，并且 通过释放三磷酸腺苷来启动传导的血管扩张剂反应， 实现氧气供应与需求的适当匹配。三个基本要素 将使用以下方法来评估这一假设：1)使用孤立的 金黄地鼠牵拉肌小动脉与红细胞灌流的关系 将评估低外腔PO2、ATP释放和血管直径；2) 三磷酸腺苷诱导的血管扩张在上游进行的机制 将沿着微血管系统进行研究；以及3) 囊性纤维化跨膜电导调节因子及其相关蛋白 红细胞释放三磷酸腺苷的信号转导途径是 下定决心。这些发现将被合并到一个生理模型中 调节血流分布以满足组织需求的模型 这将填补长期追逐的代谢调节剂的角色 血流分布。

DESCRIPTION: (Adapted from the Investigator's Abstract) The goal of this project is to substantiate a role for the red blood cell (RBC) in the regulation of microvascular perfusion in the peripheral microcirculation. The appropriate matching of oxygen supply to demand requires a sensor of tissue oxygen need, and effector of alterations in oxygen supply to meet those needs. The P.I. s earlier studies have indicated that RBC oxygen content is more important than partial pressure of oxygen, pO2, for the maintenance of capillary oxygen supply in severe hypoxia. Since the only portion of the oxygen transport pathway directly influenced by oxygen content is the hemoglobin in the RBC, it was suggested that the RBC must be involved in sensing oxygen demand and altering blood flow appropriately. The level of oxygen content of the RBC's in blood vessels at a particular point in the tissue is directly linked to the level of oxygen utilization by the tissue. If the mobile RBC were able to sense oxygen need and bring about decreases in vascular caliber, this would provide an efficient means of increasing blood flow and oxygen delivery wherever and whenever the need might arise. This would eliminate the need for a diverse network of sensing sites throughout the vasculature. Since ATP is present in RBCs, which is released in response to low pO2 and low pH, and when applied intraluminally into arterioles and venules induces a conducted vasodilator response, it was hypothesized that the RBC is a sensor of tissue oxygen requirements, and an initiator of a conducted vasodilator response via its release of ATP, which enables the appropriate matching of oxygen supply with demand. Three basic approaches will be used to evaluate this hypothesis: 1) Using isolated RBC-perfused hamster retractor muscle arterioles, the relationship between low extraluminal pO2, ATP release and vessel diameter will be evaluated; 2) The mechanisms by which the ATP-induced vasodilation is conducted upstream along the microvasculature will be investigated; and 3) The role of the cystic fibrosis transmembrane conductance regulator (CFTR) and associated signal transduction pathways in the release of ATP from the RBC will be determined. These findings will be combined into a physiological model for the regulation of blood flow distribution to meet tissue needs, a model which would fill the role of the long sought after metabolic regulator of blood flow distribution.