Perfusion-dependent induction of de novo synthesis of renal phosphatide acyl hydrolase in ureter-obstructed rabbit kidney

Perfusion of rabbit kidney ex vivo, removed 72 h after ureter obstruction, results in a dose-dependent increase in bioassayable prostaglandin E₂ (PGE₂). In addition, there are progressive increases in PGE₂ release with time and by 5 h of perfusion, there is a markedly enhanced PGE₂ release in response to bradykinin. Previous work has demonstrated that this increased basal and hormone-stimulated PGE₂ biosynthesis is in part dependent on de novo synthesis of cyclooxygenase. Measurement of arachidonic acid released into the venous effluent as a marker of renal phosphatide acyl hydrolase activity following bradykinin stimulation of the perfused kidneys showed dose-dependent release of arachidonic acid that was markedly enhanced by 5 h of perfusion. Kidneys removed from normal rabbits exhibited dose-dependent release of arachidonic acid in response to bradykinin with no enhancement by 5 h of perfusion. The ureter-obstructed kidney exhibited a time-dependent enhanced arachidonic acid release reflecting increase phosphatide acyl hydrolase activation, which was inhibitable by cycloheximide, thus suggesting that the enhanced arachidonate release was dependent on de novo synthesis of phosphatide acyl hydrolase. Thus, perfusion of the hydronephrotic kidney apparently results in the simultaneous induction of new protein synthesis of phosphatide acyl hydrolase, cyclooxygenase, and thromboxane synthetase.