URETERAL OBSTRUCTION ENHANCES EICOSANOID PRODUCTION IN CORTICAL AND MEDULLARY TUBULES OF RAT KIDNEYS

We examined prostaglandin (PG) E-2, 6-keto PGF(1 alpha), and thromboxa ne B-2 (TxB(2)) production in cortical and medullary tubules from sham -operated control (SOC) rats and rats with bilateral ureteral obstruct ion (BUG) of 24 h duration. In SOC rats medullary tubules produced sig nificantly greater amounts of the three eicosanoids than cortical tubu les. Again, the production of PGE(2), 6-keto PGF(1 alpha), and TxB(2) by cortical and medullary tubules was significantly greater in BUO rat s than in SOC rats. To elucidate the mechanisms involved, we examined the activity of phospholipase A(2) (PLA(2)) reactive against phosphati dylcholine or phosphatidylethanolamine (PE), the activity of phospholi pase C (PLC), and the levels of cyclooxygenase (COX) in cortical and m edullary tubules from SOC and BUO rats. In SOC rats the activity of ph osphatidylcholine-PLA(2) and PE-PLA(2), the activity of PLC, and the m ass of COX were significantly greater in medullary tubules than in cor tical tubules. On the ether hand, the activity of PLC in membranes of cortical tubules and the activity of PE-PLA(2) and PLC in membranes of medullary tubules, which were in active location, were significantly greater in BUO rats than in SOC rats. COX levels were also significant ly greater in cortical and medullary tubules of BUO rats than in these of SOC rats. Thus, we indicate that medullary tubules from SOC rats h ave greater production of eicosanoids through increased activity of th e PLA(2) and PLC-COX pathway than cortical tubules from the same group of rats. Again, in rats with BUO, the tubular eicosanoid production m ay be enhanced via activation of the PLC-COX pathway in cortical tubul es or through activation of the PE-PLA(2) and PLC-COX pathway in medul lary tubules. The enhanced production of tubular eicosanoids observed in rats with BUO may affect tubular function, particularly sodium and water reabsorption.