Shimizu T, Itoh T, Nakamura M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Pharmacol Exp Ther. 1989 Aug;250(2):659-66.
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.
为了验证新型促尿酸排泄的髓袢利尿药S - 8666在远端小管有额外的作用位点，我们研究了S - 8666在速尿诱导的大鼠利尿过程中的附加利尿作用。静脉推注S - 8666（3 - 30毫克/千克）和三氯噻嗪（TCM）（1 - 10毫克/千克）在速尿诱导的利尿过程中（初始剂量，静脉注射10毫克/千克；维持剂量，静脉注射10毫克/千克/小时）导致钠排泄呈剂量依赖性增加，而注射速尿（5毫克/千克）则没有这种作用。每种药物注射后钙排泄均减少。在所有剂量的S - 8666和TCM中均观察到钙/钠显著降低。S - 8666组的额外利钠和降钙作用低于TCM组。从这些观察结果我们得出结论：1）S - 8666具有与速尿相加的利钠作用；2）S - 8666减弱了速尿的排钙作用；3）S - 8666可能在远端小管有额外的作用位点。
