Enhancement of Urine Prostaglandin Excretion by Chlorazanil in Dogs

Abstract

In conscious dogs chlorazanil (2.5 mg/kg i.v.) markedly enhanced (5-10 fold) urinary excretion of prostaglandins E2 and F2.alpha.. The effect came to a peak at 15-30 min following the administration. Chlorazanil did not modify renal blood flow or inulin clearance in non-pretreated or indomethacin pretreated dogs and the plasma renin activity remained unchanged. A marginal natriuretic and antikaliuretic activity by chlorazanil was similarly observed in non-pretreated dogs and dogs pretreated with indomethacin. The possible effects of the prostaglandins released by chlorazanil remained obscure. In vitro chlorazanil (10-4 M) exhibited a moderate inhibition of 15-OH-prostaglandin dehydrogenase but an enhanced excretion of 15-keto-13, 14-dihydro PGF2.alpha. in vivo suggested that chlorazanil increased renal prostaglandin activity by increased prostaglandin synthesis, probably due to increased precursor availability. This was presumably mediated by some as yet unknown factor since chlorazanil (4 .times. 10-5 M) failed to affect the release of precursor and prostaglandins from isolated Krebs-Henseleit perfused rabbit kidneys.