The mechanism of polyuria in rats pretreated with lithium studies by in vitro microperfusion.
The collecting ducts in papillae taken from normal rats have a measurable increase in diffusional tritiated water (THO) permeability with ADH 5 mu unit/ml and this increase is maximal with antidiuretic hormone (ADH) 100 mu unit/ml added to media. The presence of plasma from rats pretreated with lithium to make them polyuric inhibited the response to ADH. The lowest concentration of ADH that caused a measurable increase in diffusional water permeability was 50 mu unit/ml and the increase was maximal with ADH 2000 mu unit/ml. The maximum response to ADH did not differ whether plasma from control or lithium pretreated rats was used. However, the dose-response curve to ADH was shifted to the right by the plasma from lithium-pretreated rats. Lithium added to the plasma from control rats did not alter the response to ADH. It is proposed that lithium given to rats causes a circulatory factor to be produced that inhibits in a competitive fashion the response of the collecting duct to ADH. Such an effect would explain many features of the impairment of water excretion associated with lithium use.
D000818:Animals; D001834:Body Water / Q000187:drug effects; D003919:Diabetes Insipidus / Q000378:metabolism*; D004231:Diuresis / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D008094:Lithium