ERYTHROCYTE--A REGULATOR OF MICROVASCULAR PERFUSION

红细胞——微血管灌注的调节者

• 批准号: 2839040
• 负责人: MARY L ELLSWORTH
• 金额: $ 15.55万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839040
• 关键词: adenosine triphosphate; capillary; chloride channels; erythrocytes; hamsters; hemoglobin; laboratory rabbit; microcirculation; oxygen tension; oxygen transport; vasomotion

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.

描述：（根据调查员的摘要进行了改编） 项目将证实红细胞（RBC）在 调节周围微循环中微血管灌注。 氧气供应与需求的适当匹配需要一个传感器 组织氧的需求和氧气供应改变的效果因素满足 这些需求。 P.I. S先前的研究表明RBC氧气 含量比氧气的部分压力PO2重要 维持严重缺氧的毛细血管供应。 从唯一的 直接影响氧气影响的氧运输途径的一部分 内容是RBC中的血红蛋白，建议RBC必须是 参与感测氧的需求并适当地改变血液。 rbc在血管中的氧气含量水平在特定的血管中 组织中的点直接与通过 组织。 如果移动RBC能够感觉到氧气需求并带来 关于血管口径的降低，这将提供有效的手段 随时随地增加血流和氧气的增加 可能会出现。 这将消除对感应的多样化网络的需求 整个脉管系统的地点。 由于RBC中存在ATP，这是 响应低PO2和低pH值，并在肿瘤内应用 进入小动脉和静脉诱导了进行的血管扩张剂反应，它是 假设RBC是组织氧的传感器，并且 通过其释放ATP的引发器进行了血管扩张剂的响应，该响应 使氧气供应与需求相匹配。 三个基本 方法将用于评估这一假设：1）使用孤立 rbc渗透的仓鼠牵开肌动脉， 将评估低腔外PO2，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 沿微脉管系统将进行研究； 3） 囊性纤维化跨膜电导调节剂（CFTR）和相关 从RBC释放ATP中的信号转导途径将为 决定。 这些发现将合并为一个生理模型 血流分布的调节以满足组织需求，一个模型 这将填补长期追求的代谢调节剂的作用 血流分布。