ERYTHROCYTE--A REGULATOR OF MICROVASCULAR PERFUSION

描述：（改编自研究者摘要）本研究的目标 该项目旨在证实红细胞 (RBC) 在 外周微循环中微血管灌注的调节。 氧气供应与需求的适当匹配需要一个传感器 组织氧需求，以及改变氧供应的效应器以满足 那些需求。 P.I.早期的研究表明红细胞氧 含量比氧分压 pO2 更重要，对于 严重缺氧时维持毛细血管供氧。 由于唯一 直接受氧气影响的氧气运输途径的一部分 含量是红细胞中的血红蛋白，因此建议红细胞必须是 参与感知需氧量并适当改变血流。 特定条件下血管中红细胞的氧含量水平 组织中的点与氧气利用水平直接相关 组织。 如果移动红细胞能够感知氧气需求并带来 关于血管口径的减小，这将提供一种有效的手段 无论何时何地需要增加血流量和氧气输送 可能会出现。 这将消除对多样化传感网络的需求 遍布脉管系统的部位。 由于 ATP 存在于红细胞中， 响应低 pO2 和低 pH 值而释放，并且在管腔内应用时 进入小动脉和小静脉诱导传导性血管舒张反应， 假设红细胞是组织需氧量的传感器， 通过释放 ATP 引发血管舒张反应， 实现氧气供应与需求的适当匹配。 三基本 方法将用于评估该假设：1）使用孤立的 红细胞灌注仓鼠牵开肌小动脉，之间的关系 将评估低腔外氧分压、ATP 释放和血管直径； 2） ATP 诱导的血管舒张在上游进行的机制 将沿着微脉管系统进行研究； 3) 的作用 囊性纤维化跨膜电导调节因子 (CFTR) 及相关 红细胞释放 ATP 的信号转导途径 确定。 这些发现将被整合到一个生理模型中 调节血流分布以满足组织需求的模型 这将填补长期以来备受追捧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.