Greven J, Farjam A
Abteilung Pharmakologie der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen, Federal Republic of Germany.
Pflugers Arch. 1988 May;411(5):579-83. doi: 10.1007/BF00582381.
Inhibitors of prostaglandin synthesis such as indomethacin and meclofenamate may attenuate the diuretic response to furosemide. The purpose of the present study was to clarify whether an inhibition of furosemide's action in the loop of Henle is involved in this interaction. In a first set of experiments, the effect of indomethacin and meclofenamate on the diuretic response to furosemide was re-evaluated in anaesthetized rats. Single loops of Henle of rat kidneys were perfused in vivo in a second group of rats. Furosemide was added to the perfusion fluid and the effect of indomethacin (5 mg/kg i.v.) and meclofenamate (5 mg/kg i.v.) on furosemide's action in the loops was tested. In the absence of furosemide, indomethacin and meclofenamate did not significantly affect urine flow and sodium chloride excretion, or the loop's sodium and chloride reabsorption. Both prostaglandin inhibitors, however, significantly attenuated the diuretic effect of furosemide (1 mg/kg i.v.) and the inhibitory action of the diuretic, at a concentration of 10(-4) M, on the loop's sodium and chloride transport. The results identify the loop of Henle as a tubular site of interaction between furosemide and prostaglandin inhibitors. The interaction may be related to a furosemide-induced stimulation of renal prostaglandins.
前列腺素合成抑制剂，如吲哚美辛和甲氯芬那酸，可能会减弱呋塞米的利尿反应。本研究的目的是阐明在髓袢中对呋塞米作用的抑制是否参与了这种相互作用。在第一组实验中，在麻醉大鼠中重新评估了吲哚美辛和甲氯芬那酸对呋塞米利尿反应的影响。在第二组大鼠中对大鼠肾脏的单个髓袢进行体内灌注。将呋塞米加入灌注液中，并测试吲哚美辛（5毫克/千克静脉注射）和甲氯芬那酸（5毫克/千克静脉注射）对髓袢中呋塞米作用的影响。在没有呋塞米的情况下，吲哚美辛和甲氯芬那酸对尿流量、氯化钠排泄或髓袢的钠和氯重吸收没有显著影响。然而，两种前列腺素抑制剂均显著减弱了呋塞米（1毫克/千克静脉注射）的利尿作用，以及在浓度为10⁻⁴M时利尿剂对髓袢钠和氯转运的抑制作用。结果表明髓袢是呋塞米与前列腺素抑制剂之间相互作用的肾小管部位。这种相互作用可能与呋塞米诱导的肾前列腺素刺激有关。
