P-450 Eicosanoids: A Novel Signaling Pathway Regulating Renal Function

Cytochrome P-450 enzymes primarily metabolize arachidonic acid to epoxy-eicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) in the kidney. These compounds serve as second messengers that play a central role in the regulation of renal vascular tone and sodium reab-sorption in the proximal tubule and thick ascending loop of Henle. It has long been recognized that cyclooxygenaseand lipoxygenase enzymes metabolize arachi-donic acid (AA) in the kidney and that the prod-ucts formed influence both renal tubular and vas-cular function (3, 8). However, in the last 10 years, a new pathway for the renal metabolism of AA has emerged. Indeed, recent studies indicate that in the renal vasculature, glomerulus, proximal tubule (PT), and thick ascending limb of the loop of Henle (TALH), AA is primarily metabo-lized by cytochrome P-450 enzymes to epoxy