Effect of prostaglandin inhibition on demeclocycline administration in conscious rats

Studies were performed in conscious rats to evaluate the role of renal prostaglandin biosynthesis in demeclocycline-induced polyuria. Three groups of animals were evaluated. Group 1 animals received only the diluents used for both demeclocycline and indomethacin. Group 2 received demeclocycline (20 mg/kg/day) and the indomethacin diluent. Group 3 received both demeclocycline and indomethacin (10 mg/kg/day). After eight days of demeclocycline administration, urine flow rate increased in the group 2 animals from 15.1 +/- 2.1 to 31.1 +/- 5.1 ml/day. Indomethacin failed to alter the magnitude of demeclocycline-induced polyuria despite a 60% reduction in urine prostaglandin E excretion rats. These studies demonstrate that the concentrating defect induced by demeclocycline can occur independent of alterations in praostaglandin biosynthesis and suggest that a change in renal prostaglandin biosynthesis is not an etiologic factor in demeclocycline-induced polyuria.