This proposal is directed at an assessment of the biological role of the arachidonate products of arachidonic acid metabolism on kidney function. We propose to correlate changes in endogenous synthesis to alterations in function that may occur in such forms of renal injury as unilateral and bilateral ureteral obstruction, glycerol induced experimental renal failure and mercuric chloride induced acute renal failure. In addition, the potential of leukochemotactic factors of the lipoxygenase pathway as mediators of glomerular injury and permselectivity will be investigated. We will therefore measure the functional parameters of renal blood flow, urinary electrolyte excretion urinary concentration ability and simultaneous alterations in endogenous synthesis and release into renal venous blood and urine of products of cyclooxygenase and lipoxygenase pathway. We will also assess the effects of products of the lipoxygenase and cytochrome P450 pathways on sodium and water transport in isolated anuran membranes. In addition we will attempt to determine the effects of the leukochemotactic factors of the lipoxygenase pathway on glomerular permselectivity in vivo. Finally in order to achieve these goals we much utilize the sensitive analytical tools of gas chromatography mass spectrometry. The methods will involve synthesis of deuterated internal standards, the ability to measure primary prostaglandins, their metabolites and products of the lipoxygenase pathway in biological fluids e.g. serum, urine. Chromatography, purification and ability to confirm structural purity and to perform measurements by mass ion detection will be the essential methodology required for completion of the projects outlined.
