Dissociation between renal medullary PGE2-synthesis and urine PGE2-excretion. Antagonism by bumetanide of chlorazanil induced urine PGE2-excretion in rats.

Normal conscious female Sprague-Dawley rats were treated with chlorazanil (3 mg/kg i.p.), and urine was collected for 3 hours. Urine prostaglandin E2-excretion increased from 25 +/- 3 to 271 +/- 32 ng/kg/3 h. The enhancement of urine PGE2-excretion was inhibited by pretreatment with bumetanide (75 mg/kg p.o.). In separate experiments the papillary quantity of PGE2 was determined in freshly homogenized tissue. The basal level (14 +/- 2 ng PGE2/papilla) was increased by chlorazanil to 51 +/- 11 ng PGE2/papilla and 24 +/- 7 ng PGE2/papilla at one and two hours respectively after drug administration. The capacity of chlorazanil to increase medullary PGE2 accumulation was unaffected by bumetanide pretreatment. The results show that bumetanide dissociated the medullary PGE2 level from the excretion of PGE2 in urine, when the former was elevated by chlorazanil.