Local mechanisms, that act upon the microvasculature, control blood flow to various 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 the influence of disease states on the microcirculation can be understood, 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, the precise role in the local control of blood flow is unclear because we do not know 1.) the location of the sensor that mediates microvascular oxygen reactivity and 2.) the mechanism of action of oxygen on the microvasculature. These two areas are the foci of this proposal. We have the unique ability to critically evaluate hypotheses concerning oxygen and control of microvascular function by the use of state of the art techniques such as intravital videomicroscopy, in situ microvessel perfusion, cannulation of isolated arterioles, and measurement of PO2 with oxygen microelectrodes. These methods will be used in the research proposed in this application to determine the location of the sensor that mediates arteriolar oxygen reactivity and to examine the mechanism of action of oxygen on arterioles. We will test the hypotheses that: 1.) the oxygen sensors that mediate arteriolar oxygen reactivity are located in venules and involve leukocytes in hamster cheek pouches, but are in arterioles in hamster striated muscle, 2.) the 5-lipoxygenase and leukotrienes mediate a portion of arteriolar oxygen reactivity in the hamster cheek pouch, but not in hamster striated muscle, and 3.) adenosine triphosphate (ATP)-sensitive K+ channels determine tone, vasodilator reactivity, and oxygen sensitivity of arterioles in hamster microcirculatory beds. These experiments will be carried out on the cheek pouch and cremaster muscle of golden Syrian hamsters.
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