Water metabolism after cisplatin in the rat.
A polyuric state is often observed after cis-dichlorodiammine platinum (cisplatin). To study the mechanism of this polyuria we gave 5-6 mg/kg cisplatin to conscious rats and observed polydipsia and a polyuric form of mild acute renal failure. A defect in renal concentrating ability was observed 1 and 8 days after cisplatin. Animals demonstrated diminished postdehydration plasma vasopressin at 1 but not at 8 days after cisplatin, and exogenous vasopressin corrected the renal concentration defect at 1 but not at 8 days after cisplatin. To assess the role of polydipsia in the concentration defect, water intake in cisplatin-treated animals was matched to pair-fed controls. Prevention of polydipsia improved the polyuria but not the concentration defect seen 8 days after cisplatin. To assess intrarenal factors in the renal concentration defect, postdehydration interstitial solute was measured and was significantly lower in cisplatin-treated than in control animals. To determine whether the diminished interstitial solute was due to vascular mechanisms, inner medullary plasma flow was measured and was identical in cisplatin-treated and control rats. Treatment with cisplatin also resulted in decreased excretion of a water load. We conclude that either impaired synthesis or release of vasopressin is the cause of the impaired renal concentration seen 1 day after cisplatin. Eight days after cisplatin, the renal concentration defect is due in part to decreased interstitial tonicity.
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D001834:Body Water / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D015232:Dinoprostone; D004326:Drinking; D007444:Inulin / Q000378:metabolism; D007679:Kidney Medulla / Q000502:physiology / Q000503:physiopathology; D008297:Male; D011141:Polyuria / Q000503:physiopathology*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology*; D010130:p-Aminohippuric Acid / Q000378:metabolism
D011458:Prostaglandins E; D014667:Vasopressins; D001127:Arginine Vasopressin; D007444:Inulin; D015232:Dinoprostone; D002945:Cisplatin; D010130:p-Aminohippuric Acid