Arachidonic acid is converted to cascade of biologically active metabolities. These derivatives include both cyclooxygenase products, eg. bisenoic prostaglandins, prostacyclin and thromboxane; as well as the newly discovered lipoxygenase metabolites, leukotrienes. These lipids exhibit a wide spectrum of actions and interact with a variety of hormonal systems resulting in a wide range of complex influences. Peripheral vascular actions of arachidonate and cyclooxygenase metabolites have been studied extensively, yet it has not been possible to firmly establish a role for these derivatives in regulation of peripheral regional hemodynamics. Major goals of the propsoed research project are to improve our understanding of the role of these naturally occurring substances in regulation of vascular resistance and regional distribution of blood flow. These studies will be carried out in in vivo animal models under conditions of natural blood flow. Noncannulating electromagnetic flow probes will be used to measure flow. Studies will be carried out to determine whether arachidonic acid metabolism is altered in an in vivo model of hydroneohrosis, since such a model may represent a novel means of investigating the function of arachidonic acid derivatives in circulatory control. Studies will also be carried out to determine whether lipoxygenase metabolites are formed in this model, and whether these derivatives possess the capacity to participate in hemodynamic control mechanisms. Additionally, potentially altered hemodynamic influnces of prostaglandins in the obstructd kidney will be determined. Overall knowledge gained from these studies will improve our understanding of the role of these potent endogenous substances in control of the peripheral vascular bed, and should provide insights into treatment of diseases such as essential hypetension.
