Emmanouel D S, Lindheimer M D, Katz A I
J Clin Invest. 1974 Oct;54(4):926-34. doi: 10.1172/JCI107833.
The ability to excrete an oral water load and the renal diluting mechanism were studied in hypothyroid rats and in age-matched euthyroid controls. Hypothyroid animals excreted a significantly smaller fraction of a 50-ml/kg oral water load than controls, demonstrating the same limited ability to excrete free water as thyroid-deficient man. During hypotonic (0.45%) saline infusion, absolute sodium delivery to the diluting segment and free water clearance were markedly lower in hypothyroid rats. However, both fractional distal sodium delivery and fractional free water clearance were similar in hypothyroid and control animals, suggesting that the reduced absolute free water formation in hypothyroid rats was due to decreased net distal delivery. In support of this hypothesis was the observation that fractional distal sodium reabsorption was equal or higher in thyroid-deficient rats, which indicates that the sodium reabsorptive capacity of the diluting segment was preserved in these animals. The results cannot be attributed to incomplete suppression of antidiuretic hormone (ADH) since they were identical in diabetes insipidus rats, nor to different rates of non-ADH-dependent backflux of filtrate since tissue osmolality and solute concentrations in the cortex, medulla, and papilla were similar in hypothyroid and control rats of both Sprague-Dawley and Brattleboro strains. The functional integrity of the diluting segment in hypothyroid rats was further demonstrated in experiments in which distal delivery was increased by contralateral nephrectomy or by administration of carbonic anhydrase inhibitors which decrease proximal sodium reabsorption. In both studies, fractional free water clearance increased markedly reaching levels significantly greater than in euthyroid controls. These results demonstrate that the impaired ability of the hypothyroid rat to excrete a water load is not due to incomplete suppression of ADH or decreased reabsorptive capacity of the diluting segment but results from decreased filtrate delivery to this site secondary to reduced GFR.
对甲状腺功能减退大鼠和年龄匹配的甲状腺功能正常对照大鼠的口服水负荷排泄能力及肾脏稀释机制进行了研究。甲状腺功能减退动物排泄50ml/kg口服水负荷的比例明显低于对照组，这表明其排泄自由水的能力与甲状腺功能减退的人类一样有限。在输注低渗（0.45%）盐水期间，甲状腺功能减退大鼠输送到稀释段的绝对钠量和自由水清除率明显较低。然而，甲状腺功能减退和对照动物的远端钠输送分数和自由水清除分数相似，这表明甲状腺功能减退大鼠绝对自由水生成减少是由于远端净输送减少所致。支持这一假设的观察结果是，甲状腺功能减退大鼠的远端钠重吸收分数相等或更高，这表明这些动物稀释段的钠重吸收能力得以保留。这些结果不能归因于抗利尿激素（ADH）抑制不完全，因为在尿崩症大鼠中结果相同，也不能归因于非ADH依赖的滤液回流速率不同，因为斯普拉格-道利和布拉特洛伯罗品系的甲状腺功能减退和对照大鼠的皮质、髓质和乳头中的组织渗透压和溶质浓度相似。在通过对侧肾切除术或给予减少近端钠重吸收的碳酸酐酶抑制剂来增加远端输送的实验中，进一步证明了甲状腺功能减退大鼠稀释段的功能完整性。在这两项研究中，自由水清除分数均显著增加，达到明显高于甲状腺功能正常对照的水平。这些结果表明，甲状腺功能减退大鼠排泄水负荷能力受损并非由于ADH抑制不完全或稀释段重吸收能力降低，而是由于肾小球滤过率降低导致输送到该部位的滤液减少所致。
