Polyuria of thyrotoxicosis: downregulation of aquaporin water channels and increased solute excretion.

Thyrotoxicosis is a common disorder causing cardiovascular and renal irregularities. In this study, thyrotoxicosis was produced in rats by 14 days of daily thyroxine injection. This was associated with an increase in cardiac index, mean arterial pressure, and renal blood flow compared with euthyroid controls. Food and water intake along with urine output were significantly increased in the thyrotoxic rats compared with control animals associated with a significant increase in solute excretion. Polyuria and increased solute excretion still occurred even when food and water intake was equivalent. These renal responses were associated with significant decreases in AQP1 and AQP2 water channel expression in both the ad lib and paired intake studies in the cortex and inner medulla. The downregulation of AQP2 protein occurred in spite of equivalent plasma arginine vasopressin (AVP) in the ad lib and increased AVP in the paired feeding studies. Solute-free water reabsorption was greater in both the ad lib and paired thyrotoxic than euthyroid rats and was associated with increased Na-K-2Cl cotransporter expression. We propose that the AVP-independent downregulation of AQP2, the observed increase in renal arterial pressure, and decrease in filtration fraction contribute to polyuria the increased solute excretion in spite of enhanced ion transporters in thyrotoxicosis.