Cox P G, Moons M M, Slegers J F, Russel F G, van Ginneken C A
Department of Pharmacology, University of Nijmegen, The Netherlands.
J Pharmacol Methods. 1990 Sep;24(2):89-103. doi: 10.1016/0160-5402(90)90020-l.
An isolated perfused rat kidney (IPK) preparation is described in which renal perfusion flow, perfusion pressure, urinary flow, urinary pH, and glomerular filtration rate (GFR) are recorded continuously during the perfusion experiment. The usefulness of this IPK system in studying the renal handling and the effects of non-steroidal antiinflammatory drugs (NSAIDs) is shown using salicyluric acid (SU), salicylic acid (SA), and naproxen (NA). Excretion of SU involves glomerular filtration, active secretion, and passive reabsorption. The excretion rates of SA and NA were both much lower than their filtration rate, indicating extensive reabsorption. All three drugs accumulate in the IPK but at different levels. SU accumulates much more than either SA or NA. The effects on renal function were different for the three drugs studied. SU had no effect on kidney function. SA perfusate concentrations greater than 100 micrograms/mL caused diuresis and natriuresis, while SA concentrations less than 100 micrograms/mL did not influence kidney function. NA perfusate concentrations ranging from 0.16 to 25 micrograms/mL caused a decrease in urinary flow and sodium excretion. Very high NA concentrations (greater than 500 micrograms/mL) caused an increase in urinary flow and sodium excretion. We conclude that the IPK is a suitable preparation for characterizing and comparing renal handling and effects of NSAIDs.
本文描述了一种离体灌注大鼠肾脏（IPK）制备方法，在灌注实验过程中可连续记录肾灌注流量、灌注压力、尿流量、尿pH值和肾小球滤过率（GFR）。使用水杨尿酸（SU）、水杨酸（SA）和萘普生（NA）展示了该IPK系统在研究肾脏处理以及非甾体抗炎药（NSAIDs）作用方面的实用性。SU的排泄涉及肾小球滤过、主动分泌和被动重吸收。SA和NA的排泄率均远低于其滤过率，表明存在广泛的重吸收。这三种药物在IPK中均有蓄积，但水平不同。SU的蓄积量远高于SA或NA。所研究的三种药物对肾功能的影响各不相同。SU对肾功能无影响。SA灌注液浓度大于100微克/毫升时会引起利尿和利钠作用，而SA浓度小于100微克/毫升时不影响肾功能。NA灌注液浓度在0.16至25微克/毫升范围内会导致尿流量和钠排泄减少。非常高的NA浓度（大于500微克/毫升）会导致尿流量和钠排泄增加。我们得出结论，IPK是一种适用于表征和比较NSAIDs肾脏处理及作用的制备方法。
