ERYTHROCYTE--A REGULATOR OF MICROVASCULAR PERFUSION

红细胞——微血管灌注的调节者

• 批准号: 2471531
• 负责人: MARY L ELLSWORTH
• 金额: $ 20.53万
• 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/2471531
• 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：（改编自研究者摘要） 该项目是为了证实红细胞（RBC）在 调节外周微循环中的微血管灌注。 氧气供应与需求的适当匹配需要以下传感器： 组织氧气需求，以及氧气供应变化的效应，以满足 这些需求。 私家侦探早期的研究表明，红细胞氧 含量比氧分压pO 2更重要，因为 维持严重缺氧时毛细血管的氧供应。 因为唯一的 直接受氧影响的氧运输途径部分 含量是红细胞中的血红蛋白，因此建议红细胞必须 参与感知氧气需求并适当地改变血流。 血液中的氧含量是指血液中的氧含量。 组织中的点直接与氧利用水平相关， 组织。 如果移动的红细胞能够感知氧气需求， 关于血管口径的减少，这将提供一种有效的手段， 无论何时何地，只要有需要， 可能会出现。 这将消除对不同传感网络的需要 在整个脉管系统中。 由于ATP存在于RBC中， 响应于低pO 2和低pH值释放，并且当腔内施用时 进入小动脉和小静脉引起传导性血管扩张反应， 假设红细胞是组织氧需求的传感器， 通过释放ATP引发传导性血管扩张反应， 使得氧气供应与需求适当匹配。 三个基本 方法将被用来评估这一假设：1）使用孤立的 RBC灌注仓鼠牵开肌小动脉， 将评价低腔外pO 2、ATP释放和血管直径; 2） ATP诱导的血管舒张作用的上游机制 将研究沿着微血管的作用;和3） 囊性纤维化跨膜传导调节因子（CFTR）和相关的 从RBC释放ATP的信号转导途径将被 测定 这些发现将被结合成一个生理模型， 调节血流分布以满足组织需要，模型 这将填补长期寻求的代谢调节剂的作用， 血流分布