Wilson D R, Honrath U, Sonnenberg H
Kidney Int. 1983 May;23(5):711-6. doi: 10.1038/ki.1983.83.
The distal convoluted tubule is thought to be the principal site of action of thiazide diuretics, but, to our knowledge, there are no studies of their possible effects on collecting duct transport. Microcatheterization of the inner medullary collecting duct (IMCD) was carried out in rats undergoing a modest diuresis, natriuresis, and chloriuresis from hydro-chlorothiazide (2 mg/kg/hr) and in normal controls. Delivery of fluid, sodium, and chloride to the beginning of the IMCD was increased, but not significantly, while the load remaining at the papillary tip (end) of the duct was increased markedly by hydrochlorothiazide. Chloride reabsorption in the IMCD was affected most markedly; the chloride reabsorption between the beginning and end of the duct, as a fraction of the delivered load, was reduced from 70.4 +/- 5.4% in controls to insignificant amounts with hydrochlorothiazide (8.2 +/- 11.5%, P less than 0.001). The fraction of delivered sodium reabsorbed along the collecting duct was decreased from 78.5 +/- 4.9% in controls to 37.2 +/- 12.4% (P less than 0.005) in thiazide-treated rats and fluid reabsorption was decreased from 59.4 +/- 4.0% in controls to 31.9 +/- 5.1% (P less than 0.005). Small but significant potassium secretion into the IMCD occurred with hydrochlorothiazide, probably secondary to the marked increase in potassium delivery to the duct. Increased potassium excretion could account for a maximum of 50% of chloriuresis with hydrochlorothiazide. The observation that thiazide diuretics decrease chloride, sodium, and fluid reabsorption in the medullary collecting duct, like the recently demonstrated inhibitory effect of furosemide on this nephron segment, has significant implications for the rationale for diuretic use.
远曲小管被认为是噻嗪类利尿剂的主要作用部位，但据我们所知，尚无关于其对集合管转运可能产生影响的研究。对接受氢氯噻嗪（2mg/kg/小时）适度利尿、利钠和利氯作用的大鼠以及正常对照大鼠进行了内髓集合管（IMCD）的微插管实验。氢氯噻嗪使进入IMCD起始段的液体、钠和氯的输送量增加，但增加不显著，而该段管道乳头端（末端）剩余的负荷却显著增加。IMCD中的氯重吸收受到的影响最为显著；管道起始段和末端之间的氯重吸收，作为输送负荷的一部分，从对照组的70.4±5.4%降至氢氯噻嗪处理组的微不足道的水平（8.2±11.5%，P<0.001）。沿集合管重吸收的输送钠的比例从对照组的78.5±4.9%降至噻嗪处理组的37.2±12.4%（P<0.005），液体重吸收从对照组的59.4±4.0%降至31.9±5.1%（P<0.005）。氢氯噻嗪使少量但显著的钾分泌到IMCD中，这可能继发于输送到该段管道的钾显著增加。增加的钾排泄最多可占氢氯噻嗪所致利氯作用的50%。噻嗪类利尿剂减少髓质集合管中氯、钠和液体的重吸收这一观察结果，如同最近所证实的速尿对该肾单位节段的抑制作用一样，对利尿剂使用的理论依据具有重要意义。
