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.