Mechanism of increased renal prostaglandin E2 in uranyl nitrate-induced acute renal failure.
We have previously demonstrated that decreased cortical prostaglandin metabolism can contribute significantly to an increase in renal tissue levels and activity of prostaglandin E2 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 E2 metabolism (measured as both prostaglandin E2-9-ketoreductase and prostaglandin E2-15-hydroxydehydrogenase activity), and tissue concentration of prostaglandin E2 were determined in rabbit kidneys following an intravenous administration of uranyl nitrate (5 mg/kg). No changes in the rates of cortical microsomal prostaglandin E2 and prostaglandin F2 alpha synthesis were noted at the end of 1 and 3 days, while medullary synthesis of prostaglandin E2 fell by 47% after 1 day and 43% after 3 days. Cortical cytosolic prostaglandin E2-9-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 E2-15-hydroxydehydrogenase activity after 3 days. Cortical tissue levels of prostaglandin E2 increased by 500% at the end of 3 days. These data demonstrate that in nephrotoxic acute renal failure, decreased prostaglandin metabolism (i.e., prostaglandin E2-9-ketoreductase activity) can result in increased tissue levels of prostaglandin E2 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.
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism; D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D011460:Prostaglandins F / Q000096:biosynthesis; D011817:Rabbits; D014018:Tissue Distribution; D014501:Uranium; D014502:Uranyl Nitrate
D011458:Prostaglandins E; D011460:Prostaglandins F; D014502:Uranyl Nitrate; D014501:Uranium; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; C035858:prostaglandin-E2 9-reductase; D015232:Dinoprostone