Mechanism of increased renal prostaglandin E 2 in uranyl nitrate-induced acute renal failure

Abstract

We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E 2 in bilateral ureteral obstruction, a model of acute renal failure. In the present study, we have further investigated whether alterations in prostaglandin metabolism can occur in a nephrotoxic model of acute renal failure. Prostaglandin synthesis, prostaglandin E 2 metabolism (measured as both prostaglandin E 2-9-ketoreductase and prostaglandin E 2-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E 2 were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E 2 and prostaglandin F 2α synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E 2 fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E 2-9-ketoreductase activity was found to be decreased by 36% and 76% after 1 and 3 days respectively. No significant changes were noted in cortical cytosolic prostaglandin E 2-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E 2 increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E 2-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E 2 in the absence of increased prostaglandin synthesis and suggest that alterations in prostaglandin metabolism may be an important regulator of prostaglandin activity in acute renal failure.