Arachidonic acid is converted to a cascade of substances which possess a high degree of biological activity. These metabolites of arachidonic acid include prostaglandins, prostacyclin and thromboxane A2. Many studies on the vascular actions of the classical prostaglandins have been carried out, however, none of these substances has been firmly established as a physiological mediator of blood flow regulation. Thromboxane A2 and prostacyclin are two recently discovered metabolites of arachidonic acid whose actions in the peripheral regional vascular bed are not well established. Major goals of the proposed research project are to improve our understanding of the role of arachidonic acid and its oxidative metabolites in the regulation of peripheral vascular resistance and in the distribution of blood flow in the peripheral regional vascular bed. The major thrust of these studies will be to investigate the vascular actions of thromboxane A2 and prostacyclin in in vivo animal models. These studies will be carried out under conditions of both controlled and natural blood flow in the intestinal, renal and hindlimb vascular beds. Under conditions of controlled flow, changes in vascular resistance are directly reflected by changes in perfusion pressure. Electromagnetic flow probes (non-cannulating) will be used to measure blood flow in peripheral regional beds under conditions of free flow and will provide information regarding the influence of these agents on regional beds under natural physiologic conditions. Another goal of this projct is to investigate interactions of prostacyclin and inhibitors of prostacyclin formation with vasoactive hormones and sympathetic nerve stimulation in regional vascular beds. Overall knowledge gained from these studies will improve our understanding of the role of arachidonic acid and its metabolites in the control of the peripheral vascular bed, and should provide insight into the treatment of diseases such as essential hypertension.