Decreased renal prostaglandin metabolism in ureteral obstruction

Studies were performed in rabbits to assess whether alterations in renal prostaglandin metabolism occur with ureteral obstruction. After 3 days, the cortical metabolism of prostaglandin E2 (as measured by prostaglandin E2-9-ketoreductase activity) decreased by almost 40% in unilateral and 50% in bilateral ureteral obstruction when compared to appropriate control levels. Medullary prostaglandin E2 metabolism decreased by 70% after unilateral ureteral obstruction but was unchanged in response to bilateral ureteral obstruction. Enzyme kinetics data from bilateral ureteral obstructed and sham-operated kidneys revealed non-competitive inhibition. In contrast to metabolism, cortical prostaglandin E2 biosynthesis increased by 122% over the control levels in unilateral, and 205% in bilateral ureteral obstruction. However, medullary prostaglandin E2 synthesis fell by almost 40% after bilateral obstruction. These data suggest that decreased renal prostaglandin metabolism, together with increased biosynthesis, could have significant effects on local prostaglandin tissue concentrations and thus explain the enhanced activity of these lipids previously noted in this model.