Inhibition of Renal Prostaglandin Synthesis and Metabolism by Indomethacin in Rats

Summary

The effect of indomethacin and other NSAID on renal prostaglandin synthesis and metabolism was studied in nondiuretic rats prepared for acute experimentation. Thirty minutes after the administration of a 2 mg/kg iv dose of indomethacin, the concentration of prostaglandin in renal venous blood as determined by bioassay was reduced 69%. In addition, conversion of radiolabeled arachidonic acid to prostaglandin E₂ in vitro by the renal papillae of indomethacin pretreated rats was inhibited 97%.

Pretreatment with indomethacin also inhibited renal cortical-medullary prostaglandin E₂ 9-ketoreductase activity by 61%. NAD⁺-dependent 15-hydroxy-prostaglandin dehydrogenase activity was diminished 46%; however, this inhibition was not statistically significant. NADP⁺-dependent 15-hydroxy-prostaglandin dehydrogenase activity was unaffected by pretreatment. It is concluded that indomethacin alters net renal prostaglandin production by inhibiting both prostaglandin synthesis and its metabolism.