Reduced Urine Kallikrein Excretion and Antikaliuresis by Chlorazanil in Rats

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Abstract
In normal, conscious, female Sprague-Dawley rats, chlorazanil (3 mg/kg i.p.) reduced urine kallikrein excretion by .apprx. 80%. Urine kininogenase activity decreased from 54 .+-. 5 to 10 .+-. 2 U/kg per 3 h and urine TAMe[p-tosyl-1-arginine methyl ester]-esterase activity decreased from 34 .+-. 1.5 to 7.4 .+-. 1.0 mEU/kg per 3 h. Kidney kallikrein content decreased by .apprx. 50% from 0.76 .+-. 0.03 to 0.40 .+-. 0.07 U/kidney at 3 h post-treatment. Chlorazanil (3 mg/kg i.p.) increased urine Na excretion from 0.48 .+-. 0.04 to 2.48 .+-. 0.98 mmol/kg per 3 h and decreased K excretion from 1.06 .+-. 0.45 to 0.29 .+-. 0.09 mmol/kg per 3 h. Comparable antikaliuretic doses of amiloride (5 mg/kg i.p.) or triamterene (10 mg/kg orally) did not change urine kallikrein excretion. Chlorazanil inhibited kidney kallikrein synthesis possibly by an innate antimineralocorticoid-like effect.