Reversal by prostaglandin E2 infusion of the effects of indomethacin on the excretion of nitrogenous compounds in the rat.

Rats were treated with Indomethacin (Indo; 2 mg/kg/d) with or without concomitant infusion of prostaglandin (PG)E2 (100 micrograms/d) to investigate the effects of inhibition of PG synthesis and PG replacement on the urinary excretion of total nitrogenous compounds, urea and creatinine and on the plasma concentration of urea and creatinine. The results indicated: (1) Indo significantly reduced the urine excretion of nitrogen, urea and creatinine within 48 hours of drug administration. (2) This effect was reversible on stopping the drug. (3) PGE2 infusion completely reversed the effect on urine creatinine and partly reversed the effects on urinary nitrogen and urea excretion. (4) Plasma urea concentrations were reduced by Indo and remained low during PGE2 infusion whereas plasma creatinine progressively increased during the study. The results support the hypotheses: (1) that Indo reduces the renal excretion of end products of nitrogen metabolism by inhibition of endogenous PG production and (2) that production of urea and therefore protein and amino acid metabolism is altered by Indo treatment in addition to its renal action.