Early polyuria in the rat following single-dose cis-dichlorodiammineplatinum (II): effects on plasma vasopressin concentration and posterior pituitary function

Central effects associated with DDP-induced early polyuria are described. Male Sprague-Dawley rats injected intraperitoneally with DDP (5 mg/kg) have a threefold increase in urine volume in the first 24 hr after treatment. This is accompanied by a corresponding decrease in Uosm but no decrease in renal function as indicated by serum creatinine or GFR. Treated animals having free access to water have reduced levels of plasma AVP, 1.42 +/- 0.14 pg/ml compared to 2.63 +/- 0.47 for control, at 8 hr after injection, and treated animals deprived of water have decreased plasma AVP at 12 and 24 hr after injection. The early polyuria in DDP-treated animals can be prevented by the administration of exogenous AVP. At 8 hr after DDP injection, posterior pituitary AVP content is identical in treated and control rats. In vitro studies with isolated pituitaries show that DDP, either 0.85 and 1.7 mM, in the medium inhibits AVP release by 60% to 90% during two successive 10 min incubation periods. These results suggest that DDP inhibits AVP release from the posterior pituitary but has no effect on AVP synthesis. This inhibition of AVP release results in lowered plasma AVP levels, which reduces water reabsorption and causes polyuria.