Additive diuretic effect of S-8666 during furosemide-induced diuresis in rats.
In order to verify that the novel uricosuric loop-acting diuretic S-8666 has an additional site of action in the distal tubule, we investigated the additive diuretic effect of S-8666 during furosemide-induced diuresis in rats. Intravenous bolus injection of S-8666 (3-30 mg/kg) and trichlormethiazide (TCM) (1-10 mg/kg) caused dose-dependent increases in Na+ excretion during furosemide-induced diuresis (primary, 10 mg/kg i.v.; sustaining, 10 mg/kg/hr i.v.), whereas injection of furosemide (5 mg/kg) did not. Ca++ excretion was decreased by injection of each drug. A significant reduction in Ca++/Na+ was observed at all doses of S-8666 and TCM. Additional natriuretic and hypocalciuric effects were lower in the S-8666 than in the TCM group. From these observations we conclude that: 1) S-8666 has a natriuretic effect which is additive to that of furosemide; 2) S-8666 attenuates the calciuric effect of furosemide; and, 3) S-8666 may have an additional site of action in the distal tubule.
Shimizu
T
T
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Itoh
T
T
Nakamura
M
M
D000818:Animals; D002118:Calcium / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004357:Drug Synergism; D005665:Furosemide / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood / Q000652:urine; D013237:Stereoisomerism; D013449:Sulfonamides / Q000494:pharmacology*; D014237:Trichlormethiazide / Q000494:pharmacology; D014528:Uricosuric Agents / Q000494:pharmacology*
D004232:Diuretics; D013449:Sulfonamides; D014528:Uricosuric Agents; C052960:S 8666; D005665:Furosemide; D012964:Sodium; D014237:Trichlormethiazide; D002118:Calcium