SUBCUTANEOUS ADMINISTRATION OF DESMOPRESSIN AS A TEST OF MAXIMAL URINARY CONCENTRATING ABILITY IN THE FISCHER-344 RAT

Decreased maximal urinary concentrating ability after administration o f vasopressin analogs is a sensitive indicator of some forms of nephro toxicity. To evaluate the potential of subcutaneous injection of 1-dea mino-8-D-arginine vasopressin (desmopressin) as a provocative agent in testing maximal urinary concentrating ability, rats were administered desmopressin acetate subcutaneously and urine osmolality was measured . At all dosages used (3-300 ng/kg), urinary osmolality increased for the first 4 h after desmopressin administration. At dosages > 100 ng/k g, osmolality remained elevated for 8 h. The utility of desmopressin a dministration in detecting urinary concentrating defects was validated by pretreating rats with sodium fluoride and measuring maximal urine concentrating ability after administration of 100 ng/kg desmopressin. Administration of 100 or 200 mu mol sodium fluoride (NaF) intraperiton eally daily for 3 days, resulted in 55 and 60% decrease, respectively, in maximal urinary concentrating ability. In contrast, urinary excret ion of N-acetyl-beta-glucosaminidase (NAG) was not a sensitive measure of fluoride-induced nephrotoxicity.