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西氯他宁对肾功能的影响。1. 麻醉大鼠的清除率和微穿刺研究。

Effects of cicletanine on kidney function. 1. Clearance and micropuncture studies in anesthetized rats.

作者信息

Greven J

机构信息

Department of Pharmacology and Toxicology, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.

出版信息

J Pharmacol Exp Ther. 1995 Jun;273(3):1190-6.

PMID:7791090
Abstract

The purpose of our study was to analyze the effect of cicletanine on kidney function by using clearance and free flow micropuncture techniques in anesthetized rats. In the clearance experiments, cicletanine was tested at three different doses (15, 30 and 60 mg/kg i.v.). The drug dose-dependently increased urine flow, and urinary sodium and chloride excretion. Renal potassium excretion was also significantly enhanced. Cicletanine was as effective as hydrochlorothiazide regarding fractional renal sodium excretion. Mean arterial blood pressure fell after cicletanine at doses of 30 and 60 mg/kg, but at none of the three doses tested did cicletanine affect renal plasma flow and glomerular filtration rate. In this regard it differed from hydrochlorothiazide which was found to markedly decrease glomerular filtration rate at a dose of 10 mg/kg i.v. A coadministration of cicletanine (20 mg/kg i.v.) and hydrochlorothiazide, at a maximal effective dose (20 mg/kg i.v.), induced an additional diuretic and saluretic effect. By puncturing of late proximal, early and late distal nephron segments, an action of cicletanine (30 mg/kg i.v.) in the superficial distal tubule could be established. Thus, cicletanine shares with the thiazide diuretics its tubular site of action despite the disparity in chemical structure between these drugs.

摘要

我们研究的目的是在麻醉大鼠中,运用清除率和自由流微穿刺技术分析西氯他宁对肾功能的影响。在清除率实验中,对西氯他宁进行了三种不同剂量(15、30和60毫克/千克静脉注射)的测试。该药物剂量依赖性地增加尿量、尿钠和尿氯排泄。肾钾排泄也显著增强。就肾钠排泄分数而言,西氯他宁与氢氯噻嗪效果相当。静脉注射30和60毫克/千克剂量的西氯他宁后平均动脉血压下降,但在测试的三种剂量下,西氯他宁均未影响肾血浆流量和肾小球滤过率。在这方面,它与氢氯噻嗪不同,后者在静脉注射10毫克/千克剂量时会显著降低肾小球滤过率。静脉注射20毫克/千克的西氯他宁与最大有效剂量(20毫克/千克静脉注射)的氢氯噻嗪联合给药,产生了额外的利尿和促尿钠排泄作用。通过穿刺近端小管晚期、远端小管早期和晚期节段,可确定西氯他宁(静脉注射30毫克/千克)在浅表远端小管的作用。因此,尽管这些药物在化学结构上存在差异,但西氯他宁与噻嗪类利尿剂具有相同的肾小管作用部位。

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