Ray C, Carney S, Gillies A
Discipline of Medicine, Faculty of Medicine and Health Sciences, University of Newcastle, N.S.W., Australia.
Miner Electrolyte Metab. 1998;24(5):321-5. doi: 10.1159/000057390.
While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 micrometer/s), although both were relatively impermeable when compared to water. Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04 +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10(-4)) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.
虽然体内数据表明，呋塞米和氢氯噻嗪等利尿剂会改变髓质集合管（IMCD）细胞的电解质转运，但这尚未得到体内研究的证实，其机制也未得到评估。本研究评估了这些利尿剂以及氨氯吡咪对离体灌注大鼠IMCD中钠和氯单向通透性的直接影响。在没有利尿剂的情况下，钠的通透性低于氯（分别为0.63±0.05与0.83±0.08微米/秒），尽管与水相比两者的通透性都相对较低。呋塞米（10⁻⁴）和氢氯噻嗪（10⁻³）均使氯的扩散通透性增加了约30%（分别从0.80±0.06增至1.04±0.09微米/秒，p<0.01；从0.74±0.09增至0.98±0.10微米/秒，p<0.02）。然而，钠的通透性未发生改变。哇巴因或冷却（4℃）抑制Na⁺,K⁺-ATP酶可抑制基础状态下的钠通透性，但不影响氯的通透性，而最大抗利尿血管加压素（AVP）浓度不会改变钠或氯的通透性。然而，将管腔和浴液中的氯化钠浓度从150 mM增至300 mM和600 mM会显著增加钠和尤其是氯的电导。相比之下，氨氯吡咪（10⁻⁴）显著降低了钠和氯的通透性。这些研究支持了呋塞米和氢氯噻嗪对IMCD的直接作用，并表明它们在体内的作用主要是通过促进氯通过有利的电化学梯度被动进入管腔来介导的。这些结果还表明，氨氯吡咪通过与磺胺类相关利尿剂不同的机制抑制钠和氯的单向通透性。
