EFFECT OF ANGIOTENSIN-II TYPE-1 RECEPTOR ANTAGONIST ON URINARY PROSTAGLANDIN-E2 EXCRETION FOLLOWING FUROSEMIDE IN RATS

The present study was undertaken to examine an effect of an angiotensi n II type 1 (AT1) receptor antagonist on urinary prostaglandin E2 (PGE 2) excretion following furosemide, a loop diuretic, in rats. Furosemid e (30 mg/kg) was given orally with or without pretreatment with derapr il (30 mg/kg), an angiotensin converting enzyme inhibitor, TCV-116 (1 mg/kg), an AT1 receptor antagonist, or losartan (10 mg/kg), another AT 1 receptor antagonist. The 6-hour urine was collected following furose mide, and the urinary excretion of PGE2 was determined. The urinary PG E2 increased significantly following furosemide alone. However, such a furosemide-induced increase was not observed with pretreatment with d erapril, TCV-116 or losartan. These results suggest that the increased urinary excretion of PGE2 following furosemide is blunted by derapril , TCV-116 and losartan. As TCV-116 and losartan are selective AT1 rece ptor antagonists, the effect of furosemide on renal PGE2 production, a s reflected by the urinary PGE2, might be mediated by an activation of AT1 receptors.