Effects of ureteral occlusion and ethacrynic acid infusion on renal prostaglandin degradation in the dog

Abstract

The two major renal prostaglandins PGE2 and PGI2 are partly metabolized during a single passage of the kidney. To examine whether stopping glomerular filtration affected the renal degradation, PGE2 and PGI2 were infused into the suprarenal aorta of dogs during ureteral occlusion. Prostaglandin synthesis was blocked by indomethacin, 10 mg kg-1 b.w. i.v. About 20% of PGI2 and 80-90% of PGE2 were metabolized during one passage through the kidney. Prostaglandin degradation and arterial input were proportional (r greater than 0.95). Compared to control conditions at free urine flow, PGI2 degradation was not changed, whereas the degradation of PGE2 was slightly increased by ureteral occlusion. Ethacrynic acid might reduce degradation of PGE2 by inhibiting two degradation enzymes. To examine the influence of ethacrynic acid, PGE2 was infused in different doses into the suprarenal aorta of dogs before and after administration of ethacrynic acid 3 mg kg-1 b.w. i.v. At all dose levels of PGE2, 75-80% was degraded by one passage through the kidney, whether ethacrynic acid was administered or not. However, although ethacrynic acid did not alter the total renal output, the urinary fraction was reduced from 20-30% to 10-15%. We conclude that degradation of both PGE2 and PGI2 is mainly confined to the blood vessels, and that ethacrynic acid in conventional doses does not prevent degradation of PGE2, but redistributes PGE2 output from urine to renal venous blood.