Failure of infusion of prostaglandin A2 to restore the response to antidiuretic hormone in rats with polyuria induced by lithium.

Male Wistar rats were fed a lithium diet for 2--3 months producing marked polyuria (greater than 75 ml/100 g in 24 h) and a plasma Li concentration of 0.7 mmol/l. In acute experiments animals were anaesthetized with 5-ethyl-5-(1-methylpropyl)-2-thiobarbituric acid and infused with hypotonic glucose-saline (15 ml/h). Addition of prostaglandin A2 (PGA2; 0.2 ng/min) for 180 min to the infusate did not restore the impaired antidiuretic response to arginine-vasopressin (AVP) whether this agent was infused continuously (150 micromicron./min) or given as bolus injections (2500 micromicron.). In long-term experiments animals were kept in metabolism cages and Alzet osmotic minipumps were implanted for intravenous infusion of drugs at 1 microliter/h. Again, PGA2 infusion at 0.2 ng/min failed to restore the impaired antidiuretic response to AVP (150 micromicron./min). It was therefore concluded that in rats with severe polyuria induced by long-term administration of lithium, infusion of PGA2 at 0.2 ng/min cannot restore the impaired response to antidiuretic hormone as has been reported by others.