Bailey M A, Walter S J
Division of Biomedical Sciences, Imperial College School of Medicine, London, United Kingdom.
J Pharmacol Exp Ther. 1998 May;285(2):464-7.
The renal effects of glibenclamide were investigated using free flow micropuncture techniques in anesthetized Sprague-Dawley rats. Intravenous infusion of the drug (3 mg/hr) evoked a natriuresis and diuresis; potassium excretion remained unchanged. Fractional reabsorption in the proximal convoluted tubule in glibenclamide-infused rats did not differ significantly from that in control animals, although the late proximal tubular fluid to plasma concentration ratio for potassium was reduced. Fractional sodium delivery to the early distal tubule was elevated, while the fractional deliveries of water and potassium to this nephron site were unaffected. We conclude that glibenclamide impairs sodium reabsorption in one or more of the nephron segments that comprise the loop of Henle. These results are consistent with the hypothesis that the natriuresis resulting from glibenclamide administration is a consequence of blockade of potassium channels in the apical membrane of the thick ascending limb of Henle's loop. The data suggest that glibenclamide may additionally inhibit a small secretory potassium flux in the proximal tubule.
在麻醉的斯普拉格-道利大鼠中，使用自由流动微穿刺技术研究了格列本脲对肾脏的影响。静脉输注该药物（3毫克/小时）引起了利钠和利尿作用；钾排泄量保持不变。输注格列本脲的大鼠近端曲管的分数重吸收与对照动物相比无显著差异，尽管近端小管晚期钾的管腔液与血浆浓度比降低。到达早期远端小管的钠分数输送增加，而水和钾输送到该肾单位部位的分数不受影响。我们得出结论，格列本脲损害了构成亨利氏袢的一个或多个肾单位节段中的钠重吸收。这些结果与以下假设一致，即格列本脲给药引起的利钠作用是亨利氏袢厚壁升支顶端膜上钾通道被阻断的结果。数据表明，格列本脲可能还会抑制近端小管中少量的钾分泌通量。
