The effects of KW-3635 (sodium (
E)-11-[2-(5, 6-dimethyl-1-benzimidazolyl) ethylidene]-6, 11-dihydrodibenz-[b, e] oxepine-2-carboxylate monohydrate, CAS 127166-41-0), a novel thromboxane A
2 (TxA
2) receptor antagonist, on furosemide diuresis were examined in rats. After an overnight fast, the rats received either saline or drugs, and 6-hr urine samples were collected. Urine volume, urinary excretion of electrolytes and urine TxB
2 were measured. The administration of KW-3635 (10, 30 mg/kg, p.o.) or BM-13505 (10, 30 mg/kg) significantly increased the diuretic effect of furosemide (10 mg/kg, p.o.). Neither drug had any effect on urinary excretion of TxB
2. These results demonstrated that the diuretic effect of furosemide was potentiated by TxA
2 receptor blockade with KW-3635 or BM-13505. It is suggested that the diuretic effect of furosemide might be modulated by renal production of TxA
2 elicited by this drug.
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