EARLY POLYURIA IN THE RAT FOLLOWING SINGLE-DOSE CIS-DICHLORODIAMMINEPLATINUM(II) - EFFECTS ON PLASMA VASOPRESSIN CONCENTRATION AND POSTERIOR PITUITARY-FUNCTION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 100  (5) , 659-670
Abstract
Central effects associated with [the antineoplastic drug] DDP[cis-dichlorodiammineplatinum(II)]-induced early polyuria are described. Male Sprague-Dawley rats injected i.p. with DDP (5 mg/kg) have a 3-fold increase in urine volume in the first 24 h after treatment. This is accompanied by a corresponding decrease in Uosm [urine osmolality] but no decrease in renal function as indicated by serum creatinine or GFR [glomerular filtration rate]. Treated animals having free access to water have reduced levels of plasma AVP [arginine vasopressin] (1.42 .+-. 0.14 pg/ml compared to 2.63 .+-. 0.47 pg/ml for control) at 8 h after injection; and treated animals deprived of water have decreased plasma AVP at 12 h and 24 h after injection. The early polyuria in DDP-treated animals can be prevented by the administration of exogenous AVP. At 8 h 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 or 1.7 mM) in the medium inhibits AVP release by 60-90% during 2 successive 10 min incubation periods. DDP probably 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.