Mechanism of impaired water excretion in the hypothyroid rat

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.