FLOW INDUCED DILATIONS IN CEREBRAL VESSELS

血流引起的脑血管扩张

基本信息

批准号：
6330532
负责人：
ROBERT M BRYAN
金额：
$ 18.72万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-12-15 至 2001-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (Adapted from Applicant's Abstract): "Flow-induced dilation" (often referred to as "upstream dilation") of arteries and arterioles is an important mechanism for maintaining vascular homeostasis in the peripheral circulation. When blood flow increases in an artery or arteriole, the vessel dilates. This "flow-induced dilation" functions to maintain appropriate perfusion through a tissue bed by maintaining an optimum perfusion pressure across the bed. In the cerebral circulation, flow-induced effects are not well understood. In fact, there is not a consensus that flow-induced dilations even occur. The confusion and lack of consensus in the cerebral circulation could be due to multiple mechanisms responsible for flow-induced dilations. Furthermore, different mechanisms might occur at different levels of the cerebral circulatory tree. Two general hypotheses will be tested: (1) Flow-induced dilations occur at all levels of the vascular tree in the cerebral circulation (large arteries, smaller arteries, and arterioles). The mechanisms for flow-induced dilations are different at the different levels of the vascular tree. Specific hypotheses include experiments testing whether shear stress causes (a) release of an EDRF, (b) an elaboration of endothelial ATP as an autocrine/paracrine vasodilator (c) an elaboration of RBC ATP as an paracrine vasodilator (d) intravascular ATP delivery to the endothelium is a regulator of vasodilation (2) Pathological conditions such as ischemia/reperfusion impair "flow-induced dilations" at all levels of the cerebral circulatory tree. These hypothesis will be tested using isolated, pressurized, and perfused rat cerebral arteries and arterioles. The study of flow-induced dilations along the entire length of a vascular tree in a single organ is unique. Furthermore, consideration of multiple mechanisms provides a novel approach to the study of flow-induced dilations. After considering and testing these hypotheses, a clearer understanding of flow-induced effects in the cerebral circulation will be obtained. Furthermore, insight into the consequences of ischemia/reperfusion on flow-induced dilations in the cerebral circulation could lead to a therapeutic strategy for improving maintenance of cerebral perfusion after stroke.

描述（改编自申请人的摘要）：“流动诱导的扩张” （通常称为“上游扩张”）动脉和小动脉是维持外围血管稳态的重要机制循环。当血液流动在动脉或动脉中增加时，血管扩张。这种“流动引起的扩张”功能以维持通过保持最佳整个床上的灌注压力。在大脑循环中流动引起的效应尚不清楚。实际上，没有共识，即使流动引起的扩张也发生。混乱和缺乏大脑循环中的共识可能是由于多种机制负责流动诱导的扩张。此外，不同的机制可能发生在大脑循环树的不同水平。将测试两个一般的假设：（1）流动诱导的扩张发生在大脑循环中的所有血管树（大动脉，较小的动脉和动脉）。流动诱导的机制在血管树的不同水平上的扩张是不同的。特定的假设包括测试剪切应力是否原因的实验（a）释放EDRF，（b）对内皮ATP的阐述自分泌/旁分泌血管扩张剂（c）RBC ATP的详细说明旁分泌血管扩张剂（D）血管内ATP递送到内皮是一个血管舒张的调节剂（2）病理状况，例如缺血/再灌注会损害所有水平的“流动诱导的扩张” 大脑循环树。这些假设将通过孤立，加压和灌注来检验大鼠脑动脉和动脉。流动诱导的扩张的研究沿着单个器官的血管树的整个长度是独一无二的。此外，考虑多种机制提供了一种新颖的方法研究流动诱导的扩张。考虑和测试这些假设，对脑中流动诱导的影响的更清晰理解将获得循环。此外，洞悉缺血/再灌注对流动诱导的脑循环的扩张可能导致一种治疗策略来改善脑维护中风后灌注。