Effect of Cyclooxygenase-2 Inhibition on Renal Function After Renal Ablation

Kidney failure is the common end of hypertension and renal diseases. Several authors have suggested that vasodilatory prostaglandins participate in the hemodynamic mechanism responsible for the development of kidney failure. However, the mechanism by which prostaglandins are increased in renal disease is not clear. Recently, 2 isoforms of the enzyme responsible for prostaglandin synthesis, cyclooxygenase, have been described as cyclooxygenase-1 (COX-1), a constitutive isoform, and cyclooxygenase-2 (COX-2), an inducible isoform. In the present study, we investigated whether COX-2-dependent prostaglandins participate in the evolution of renal functional changes after renal ablation. We inhibited prostaglandin synthesis by COX-1 and COX-2 with indomethacin (3 mg/kg) and prostaglandin synthesis by COX-2 with NS-398 (3 mg/kg) and tested the effect of these inhibitors on the renal functional changes elicited by renal ablation. Renal ablation produced an increase in urinary volume, protein, and prostaglandin E2, whereas urinary sodium and potassium were not affected and urinary osmolarity decreased; treatment with indomethacin or NS-398 partially prevented the renal functional changes elicited by renal ablation. Immunoblots for COX showed an increase in the expression of COX-2 protein 2 days after renal ablation. Furthermore, COX-2 mRNA expression was increased 1 day after renal ablation. These data suggest that COX-2-dependent prostaglandins participate in the renal mechanisms associated with the development of renal functional changes after renal ablation.