Enhancement of Urinary Prostaglandin Excretion by Chlorazanil in Rats. Effects of Indomethacin

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Abstract
In conscious unloaded Sprague-Dawley female rats chlorazanil [a diuretic/natriuretic and antikaliuretic compound] (10 mg/kg orally) markedly increased urinary prostaglandin E2-excretion from 51 .+-. 9 to 813 .+-. 112 ng/kg per 6 h. Urinary flow rate increased from 12.8 .+-. 0.6 to 42.0 .+-. 1.4 ml/kg 6 h and urinary Na excretion from 0.96 .+-. 0.12 to 3.86 .+-. 0.33 mmol/kg per 6 h. Urinary K excretion was unchanged. Indomethacin pretreatment (5 mg/kg orally) greatly reduced the effect of chlorazanil on urinary prostaglandin E2-excretion. Indomethacin modified the excretory effects of chlorazanil, thus the enhancement of urinary flow rate was attenuated, the K excretion decreased, while Na excretion was potentiated. In non-pretreated condition chlorazanil variably affected urinary kallikrein [EC 3.4.21.8] excretion (TAMe[3H-p-tosyl-l-arginine-methyl-ester]-esterase activity) from 108 .+-. 6 to 92 .+-. 33 milli enzyme units [mEU]/kg per 6 h. After indomethacin pretreatment chlorazanil invariably reduced urine enzyme excretion from 111 .+-. 6 to 32 .+-. 4 mEU/kg per 6 h.