Increases in Glomerular Eicosanoid Production in Rats with Bilateral Ureteral Obstruction Are Mediated by Enhanced Enzyme Activities of Both the Cyclooxygenase and 5-Lipoxygenase Pathways

Abstract

Glomeruli isolated from rats with bilateral ureteral obstruction (BUO) of 24 hr duration produced significantly greater amounts of prostaglandin (PG) E₂, 6-keto-PGF_1α, thromboxane B₂, and leukotriene B₄ than glomeruli isolated from sham-operated control (SOC) rats. To examine the mechanisms underlying the greater production of eicosa-noids by glomeruli isolated from rats with BUO, we measured the activities of enzymes related to eicosanoid formation such as cyclooxygenase, 5-lipoxygenase, PGE₂ isomerase, and PGI₂ and thromboxane synthase in glomeruli isolated from SOC rats and rats with BUO. Glomeruli isolated from rats with BUO had a significantly increased activity of cyclooxygenase with de novo synthesis of this enzyme and a markedly augmented activities of PGE₂ isomerase and both PGI₂ and thromboxane synthases relative to glomeruli isolated from SOC rats. Similarly, the activity of membrane-bound 5-lipoxy-genase, the active location of this enzyme, was significantly greater in glomeruli isolated from rats with BUO than in glomeruli isolated from SOC rats. Thus, BUO of 24 hr duration enhances the glomerular production of eicosanoids via the activation of enzymes in both the cyclooxygenase and 5-lipoxygenase pathways.