César K R, Magaldi A J
Laboratório de Pesquisa Básica da Disciplina de Nefrologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo CEP 05409-003, Brazil.
Am J Physiol. 1999 Nov;277(5):F756-60. doi: 10.1152/ajprenal.1999.277.5.F756.
The reduction of urinary volume after the use of thiazide in the treatment of diabetes insipidus (DI) is known as the "paradoxical effect." Since enhanced proximal solute and water reabsorption only partially account for the reduction in urinary volume, an additional diuretic effect on nephron terminal segments was postulated. Thus the aim of our work was to investigate the effect of hydrochlorothiazide (HCTZ) on water transport in the inner medullary collecting duct (IMCD) of normal and Brattleboro rats. Osmotic water permeability (P(f)) and diffusional water permeability (P(dw)) were studied at 37 degrees C and pH 7.4 by the in vitro microperfusion technique. In the absence of antidiuretic hormone (ADH), HCTZ (10(-6) M) added to the perfused fluid enhanced P(f) from 6.36 +/- 0. 56 to 19.08 +/- 1.70 micro(m)/s (P < 0.01) and P(dw) from 38.01 +/- 4.52 to 52.26 +/- 4.38 x10(-5) cm/s (P < 0.01) in normal rats and also stimulated P(f) in Brattleboro rats from 3.53 +/- 1.41 to 11.16 +/- 1.13 micro(m)/s (P < 0.01). Prostaglandin E(2) (PGE(2)) (10(-5) M) added to the bath fluid inhibited HCTZ-stimulated P(f) (in micro(m)/s) as follows: control, 16.93 +/- 2.64; HCTZ, 29.65 +/- 5.67; HCTZ+PGE(2), 10.46 +/- 1.84 (P < 0.01); recovery, 16.77 +/- 4.07. These data indicate that thiazides enhance water absorption in IMCD from normal rats (in the absence of ADH) and from Brattleboro rats and that the HCTZ-stimulated P(f) was partially blocked by PGE(2). Thus we may conclude that the effect of thiazide in the treatment of DI occurs not only in the Na(+)-Cl(-) cotransport in the distal tubule but also in the IMCD.
使用噻嗪类药物治疗尿崩症（DI）后尿量减少被称为“反常效应”。由于近端溶质和水重吸收增强仅部分解释了尿量减少的原因，因此推测对肾单位终末节段存在额外的利尿作用。因此，我们研究的目的是探讨氢氯噻嗪（HCTZ）对正常大鼠和布拉特洛维大鼠髓质内层集合管（IMCD）水转运的影响。通过体外微灌注技术在37℃和pH 7.4条件下研究渗透水通透性（P(f)）和扩散水通透性（P(dw)）。在无抗利尿激素（ADH）的情况下，向灌注液中加入HCTZ（10(-6)M）可使正常大鼠的P(f)从6.36±0.56提高到19.08±1.70μm/s（P<0.01），P(dw)从38.01±4.52提高到52.26±4.38×10(-5)cm/s（P<0.01），并且也能使布拉特洛维大鼠的P(f)从3.53±1.41提高到11.16±1.13μm/s（P<0.01）。向浴液中加入前列腺素E2（PGE2）（10(-5)M）可抑制HCTZ刺激的P(f)（单位为μm/s），具体如下：对照组，16.93±2.64；HCTZ组，29.65±5.67；HCTZ + PGE2组，10.46±1.84（P<0.01）；恢复组，16.77±4.07。这些数据表明，HCTZ可增强正常大鼠（无ADH时）和布拉特洛维大鼠IMCD中的水吸收，且HCTZ刺激的P(f)被PGE2部分阻断。因此我们可以得出结论，噻嗪类药物治疗DI的作用不仅发生在远曲小管的Na(+)-Cl(-)共转运中，也发生在IMCD中。
