Ureteral obstruction enhances eicosanoid production in cortical and medullary tubules of rat kidneys.

Abstract

We examined prostaglandin (PG) E2, 6-keto PGF1alpha, and thromboxane B2 (TxB2) production in cortical and medullary tubules from sham-operated control (SOC) rats and rats with bilateral ureteral obstruction (BUO) of 24 h duration. In SOC rats medullary tubules produced significantly greater amounts of the three eicosanoids than cortical tubules. Again, the production of PGE2, 6-keto PGF1alpha, and TxB2 by cortical and medullary tubules was significantly greater in BUO rats than in SOC rats. To elucidate the mechanisms involved, we examined the activity of phospholipase A2 (PLA2) reactive against phosphatidylcholine or phosphatidylethanolamine (PE), the activity of phospholipase C (PLC), and the levels of cyclooxygenase (COX) in cortical and medullary tubules from SOC and BUO rats. In SOC rats the activity of phosphatidylcholine-PLA2 and PE-PLA2, the activity of PLC, and the mass of COX were significantly greater in medullary tubules than in cortical tubules. On the other hand, the activity of PLC in membranes of cortical tubules and the activity of PE-PLA2 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 significantly greater in cortical and medullary tubules of BUO rats than in those of SOC rats. Thus, we indicate that medullary tubules from SOC rats have greater production of eicosanoids through increased activity of the PLA2 and PLC-COX pathway than cortical tubules from the same group of rats. Again, in rats with BUO, the tubular eicosanoid production may be enhanced via activation of the PLC-COX pathway in cortical tubules or through activation of the PE-PLA2 and PLC-COX pathway in medullary tubules. The enhanced production of tubular eicosanoids observed in rats with BUO may affect tubular function, particularly sodium and water reabsorption.