[Effects of KW-3635 on the diuretic action of furosemide in rats].
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 A2 (TxA2) 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 TxB2 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 TxB2. These results demonstrated that the diuretic effect of furosemide was potentiated by TxA2 receptor blockade with KW-3635 or BM-13505. It is suggested that the diuretic effect of furosemide might be modulated by renal production of TxA2 elicited by this drug.
Kawakage
M
M
Pharmaceutical Research Laboratories, Kyowa Hakko Co., Ltd., Shizuoka, Japan.
Ishihara
N
N
Karasawa
A
A
Kase
H
H
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001584:Benzoxepins / Q000008:administration & dosage / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects*; D004357:Drug Synergism; D004573:Electrolytes / Q000652:urine; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000652:urine
D001562:Benzimidazoles; D001584:Benzoxepins; D004573:Electrolytes; D010648:Phenylacetates; D013449:Sulfonamides; D013928:Thromboxane A2; D005665:Furosemide; C051762:daltroban; C065729:KW 3635