THE RENAL MEDULLARY THICK ASCENDING LIMB AS A MODEL FOR UNDERSTANDINGLIPID MEDIATORS IN SEPSIS

Cytokines are an essential component in those mechanisms that depress renal function in response to inflammatory diseases of the kidney. We have addressed the role of tumor necrosis factor (TNF) in mediating ch anges in renal function by isolating a nephron segment, the medullary thick ascending limb of Henle's loop (mTAL), and studying the effects of TNF on icn transport via changes in the activity of two epoxygenase s, cyclooxygenase (COX) and cytochrome P450 (CYP450) monooxygenase. Th is nephron segment generates 20-hydroxyeicosatetraenoic acid (20-HETE) as a principal arachidonate metabolite. However, when challenged with lipopolysaccharide (LPS), the mTAL expresses a considerable capacity to metabolize arachidonic acid (AA) via a COX pathway to form PGE(2).