ROLE OF L-ARGININE IN CONTROL OF BRAIN MICROCIRCULATION

我们假设L-精氨酸在脑的控制中有两种作用 微循环 这两种作用都是内皮依赖性的， 由以下产生内皮衍生的舒张因子（“EDRF”）： 精氨酸 “EDRF”舒张血管并对抗血小板粘附 和聚合。 这些假设是基于各种出版的 数据，大部分是在体外。 假设检验将在以下方面进行： 小鼠体内软脑膜小动脉。 直径将由电视监控 显微镜 我们将测试L-精氨酸扩张小动脉的能力 而L-NMMA阻止这种扩张并收缩 小动脉 L-NMMA是L-Arg对“EDRF”的假定抑制剂。 通路 我们将比较L-Arg与其他氨基酸的活性 （对照）。 我们将用激光/伊文思蓝损伤内皮细胞 法 这消除了“EDRF”。如果L-Arg或LNMMA对 直径是内皮依赖性的，并由“EDRF”介导，这些作用 应该消失。 激光/伊文思蓝的更大损伤将诱导 受损部位血小板聚集。 我们监测 通过活体显微镜观察聚集。 我们将测试 L-Arg或L-NMMA以影响聚集的开始。 血小板 聚集在高剪切期间和之后被抑制。 我们将 看看这是否是由于试图改变“EDRF”的释放增加， 高剪切与已知改变“EDRF”释放的试剂的作用， 和LNMMA 非常轻微的内皮损伤区域消除了 局部“EDRF”而不诱导血小板聚集。 这些区域现在将 “捕获”通过的血小板栓子或由上游血管激活的血小板 刺激。 我们将尝试改变这种增加的“粘性”， 通过用已知会改变血管的物质处理血管， “EDRF”的生产或释放，以及L-Arg和LNMMA。 的作用 通过EDRF控制局部血小板聚集/粘附的L-Arg将是 支持，如果：（a）EDRF产生/释放的增强剂抑制 聚集/粘附-（B）L-Arg和LNMMA分别抑制和 增强局部聚集/粘附。

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.