Reduced urine kallikrein excretion and antikaliuresis by chlorazanil in rats.
In normal conscious female Sprague-Dawley rats chlorazanil (3 mg/kg intraperitoneally) reduced urine kallikrein excretion by approximately 80%. Thus, urine kininogenase activity decreased from 54 +/- 5 U/kg/3 hrs to 10 +/- 2 U/kg/3 hrs and urine TAMe-esterase activity decreased from 34 +/- 1.5 mEU/kg/3 hrs to 7.4 +/- 1.0 mEU/kg/3 hrs. In addition kidney kallikrein content decreased by approximately 50% from 0.76 +/- 0.03 U/kidney to 0.40 +/- 0.07 U/kidney at three hours post treatment. Chlorazanil (3 mg/kg intraperitoneally) increased urine sodium excretion from 0.48 +/- 0.04 mmol/kg/3 hrs to 2.48 +/- 0.98 mmol/kg/3 hrs and decreased the potassium excretion from 1.06 +/- 0.45 mmol/kg/3 hrs to 0.29 +/- 0.09 mmol/kg/3 hrs. Comparable antikaliuretic doses of amiloride (5 mg/kg intraperitoneally) or triamterene (10 mg/kg orally) did not change urine kallikrein excretion It is suggested that chlorazanil inhibits kidney kallikrein synthesis perhaps by an innate antimineralocorticoid-like effect.
D000450:Aldosterone / Q000502:physiology; D000818:Animals; D002722:Chlorobenzenes; D005260:Female; D007610:Kallikreins / Q000096:biosynthesis / Q000652:urine*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014227:Triazines / Q000494:pharmacology*
D002722:Chlorobenzenes; D014227:Triazines; C017837:chlorazanil; D000450:Aldosterone; D012964:Sodium; D007610:Kallikreins