Wang W, Li C, Summer S N, Falk S, Schrier R W
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Kidney Int. 2007 Nov;72(9):1088-94. doi: 10.1038/sj.ki.5002475. Epub 2007 Aug 15.
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.
甲状腺毒症是一种常见疾病，可导致心血管和肾脏功能异常。在本研究中，通过连续14天每日给大鼠注射甲状腺素诱导产生甲状腺毒症。与甲状腺功能正常的对照组相比，这与心脏指数、平均动脉压和肾血流量增加有关。与对照动物相比，甲状腺毒症大鼠的食物和水摄入量以及尿量显著增加，溶质排泄也显著增加。即使食物和水摄入量相当，仍会出现多尿和溶质排泄增加的情况。在自由进食和配对进食研究中，皮质和髓质内AQP1和AQP2水通道蛋白表达显著降低，这些肾脏反应与之相关。尽管在自由进食研究中血浆精氨酸加压素（AVP）水平相当，在配对进食研究中AVP水平升高，但AQP2蛋白仍出现下调。自由进食和配对甲状腺毒症大鼠的无溶质水重吸收均高于甲状腺功能正常的大鼠，且与钠-钾-2氯共转运体表达增加有关。我们认为，尽管甲状腺毒症时离子转运体增强，但AQP2的AVP非依赖性下调、观察到的肾动脉压升高和滤过分数降低导致了多尿和溶质排泄增加。
