The role of prostaglandins in early polyuria induced by cisplatin in the rat

To assess a possible role of prostaglandins in the early phase of cisplatin-induced abnormalities in renal concentrating ability, three groups of rats were studied. In a first group we measured prostaglandin production from renal medullary microsomes isolated from rats sacrificed at different time periods after cisplatin, 5 mg/kg alone (PB/CP) or cisplatin plus aspirin, 300 mg/kg p.o., 1 h before cisplatin and daily (ASA/CP). In a second group of rats, balance studies were performed in PB/CP and ASA/CP animals for 4 days after cisplatin to determine the effect of such treatment on the renal excretion of solute and water. In another group of rats inulin clearance was measured in PB/CP and ASA/CP animals 4 days after such treatment. The rats received aspirin or phosphate buffer alone (50 mg/ml sodium phosphate, pH 8) to determine the effect of such treatment on prostaglandin production and renal function. In PB/CPU(osm) fell and prostaglandin synthesis increased on days 1-3. Prostaglandin synthesis returned to baseline values by day 4, but U(osm) remained low. Inulin clearance was low 4 days after cisplatin. In ASA/CP rats prostaglandin synthesis did not increase and the early polyuria was ameliorated. Aspirin did not prevent the later polyuria. Inulin clearance in the ASA/CP group was markedly reduced to levels below those observed in cisplatin alone. These data demonstrate that elevated rates of prostaglandin synthesis occur early in the course of cisplatin-induced renal failure and suggest that prostaglandins may play a role in the early cisplatin-induced concentrating defect.