Local mechanisms, acting on the microvasculature, control blood flow to the body's organs to meet their metabolic demands. There is substantial evidence that disturbances in the microcirculation or local control mechanisms cause or may be caused by disease states such as hypertension and diabetes. Before we can understand the influence of such disease states on the microcirculation we must first understand the normal physiology of the system. It is well established that oxygen is involved in the regulation of microvascular function. However, its precise role in the local control of blood flow is uncertain. We have the unique ability to critically evaluate hypotheses concerning oxygen and control of microvascular function using state of the art techniques such as microvessel cannulation, preparation of parenchyma free arterioles and measurement of microvessel hemoglobin oxygen saturation. In the research propsed in this application, these methods will be used to determine the location of the oxygen sensor in the arteriolar wall and to examine the machanism of action of oxygen on arterioles. We will: 1) test the hypothesis that intravascular changes in PO2 are required for arterioles to display oxygen sensitivity and 2) test the hypothesis that metabolites of arachidonic acid, especially prostacyclin, mediate the action of oxygen on arterioles. These experiments will be carried out using in vivo microscopy in the cheek pouches of golden hamsters.
