ROLE OF L-ARGININE IN CONTROL OF BRAIN MICROCIRCULATION

L-精氨酸在控制大脑微循环中的作用

• 批准号: 3364681
• 负责人: WILLIAM I ROSENBLUM
• 金额: $ 9.57万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3364681
• 关键词: arginine; arterioles; brain circulation; cell adhesion; cell aggregation; laboratory mouse; microcirculation; microscopy; nitric oxide; vasodilators

We postulate 2 roles for L-Arginine in the control of brain microcirculation. Both roles are endothelium dependent and depend on the production of an endothelium derived relaxing factor ("EDRF") from L-Arginine. The "EDRF" relaxes the vessels and opposes platelet adhesion and aggregation. These hypotheses are based on a variety of published data, most of it in vitro. Tests of the hypotheses will be performed on mouse pial arterioles in vivo. Diameter will be monitored by TV microscopy. We will test the ability of L-Arg to dilate the arterioles and the ability of L-NMMA to block this dilation and to constrict the arterioles. L-NMMA is the putative inhibitor of the L-Arg to "EDRF" pathway. We will compare the activities of L-Arg with other amino acids (controls). We will injure the endothelium with a laser/Evans blue technique. This eliminates "EDRF". If the actions of L-Arg or LNMMA on diameter are endothelium dependent and mediated by "EDRF", these actions should be lost. A greater injury by laser/Evans blue will induce platelet aggregation at the damaged site. We monitor onset of aggregation via intravital microscopy. We will test the capacity of L-Arg or L-NMMA to influence the onset of aggregation. Platelet aggregation is inhibited during and after periods of high shear. We will see if this is due to increased release of "EDRF" by attempting to alter the effects of high shear with agents known to alter "EDRF" release and with L-Arg and LNMMA. Zones of very minimal endothelial injury eliminate local "EDRF" without inducing platelet aggregation. Such zones will now "capture" passing platelet emboli or platelets activated by an upstream stimulus. We will attempt to alter the increased "stickiness" of such "capture" sites by treating the vessels with substances known to alter production or release of "EDRF", and with L-Arg and LNMMA. A role of L-Arg in control of local platelet aggregation/adhesion via EDRF will be supported if: (a) enhancers of EDRF production/release inhibit aggregation/adhesion - (b) L-Arg and LNMMA respectively inhibit and enhance local aggregation/adhesion.

我们推测L-精氨酸在大脑控制中的两个作用 微循环。这两个角色都依赖于内皮，并依赖于 人内皮源性松弛因子(EDRF)的生产 L-阿基宁。“EDRF”松弛血管，对抗血小板黏附 和聚合。这些假说是基于各种已发表的 数据，其中大部分是体外数据。假设的测试将在以下方面进行 活体小鼠软脑膜小动脉。直径将由电视监测 显微镜。我们将测试L-Arg对小动脉的扩张能力 而L-NMMA阻止这种扩张和收缩的能力 小动脉。L-NMMA可能是L-精氨酸对内源性核转录因子的抑制作用 路径。我们将L-精氨酸与其他氨基酸的活性进行比较 (控制)。我们会用激光/伊文思蓝损伤内皮细胞 技术。这就消除了“EDRF”。如果L-arg或LNMMA在 直径是内皮依赖的，并由“EDRF”介导，这些作用 应该是迷失的。激光/伊文斯蓝造成的更大伤害将导致 受损部位的血小板聚集。我们监测到了 活体显微镜下的聚集。我们将测试其能力 L-精氨酸或L-NMMA影响聚集的开始。血小板 在高切变期间和之后，聚集被抑制。我们会 查看这是否是由于通过尝试更改 高剪切率的影响与已知的改变“EDRF”释放和 与L-arg和LNMMA。消除非常轻微的内皮损伤区域 局部“EDRF”，不会引起血小板聚集。这样的区域现在将 “捕获”通过上游激活的血小板栓子或血小板 刺激。我们将试图改变这种增加的“粘性” 通过用已知可改变的物质处理血管来“捕获”部位 制作或发行《EDRF》，并与L ARG和LNMMA合作。一个角色 L-精氨酸通过EDRF调控局部血小板聚集/黏附 在以下情况下支持：(A)EDRF产生/释放抑制的增强剂 聚集/黏附-(B)L-精氨酸和LNMMA分别抑制和 增强局部聚集/粘附性。