Molucular mechanism in the control of water metabolism : integrated study of hypothalamus and kidney

体内的水分平衡由口渴机制和下丘脑控制的加压素(AVP)释放来调节。AVP在肾脏的抗利尿作用也受到多种因素的调节。本研究从分子水平考察了下丘脑和肾脏在水稳态中的整体相关性。用c-Fos免疫组织化学方法检测大鼠下丘脑视上核内AVP细胞的神经活动。向大鼠注入高渗盐水增强了其表达，即使在其基础活性没有变化的情况下，这种反应也因出血后循环血容量的下降而被夸大。这一发现表明，AVP细胞对渗透压刺激和体积刺激都有完整的功能。在遗传性下丘脑尿崩症大鼠Brattleboro品系中，加压素依赖的水通道AQP-2的表达即使在剧烈缺水后仍保持低水平。糖皮质激素缺乏大鼠AQP-2表达增强，低钠状态下AQP-2表达减弱，分别导致尿浓缩能力增强和减弱。因此，在AVP在肾脏的作用中，AQP-2的调节在形成体内水平衡的平衡环境中起着至关重要的作用。

Water balance in the body is regulated by the thirst mechanism and vasopressin (AVP) release controlled by the hypothalamus. Antidiuretic action of AVP in the kidney is also regulated by various factors. In the present study, integrated correlation of hypothalamus and kidney in the water homeostasis was examined from the point of molecular aspects. The neural activity of AVP cells in the supraoptic nuclei in the hypothalamus was examined in rats by immuno-staining of c-Fos. Infusion of hypertonic saline to rats intensified its expression and this response was exaggerated by the fall of circulation blood volume after hemorrhage even under the absence of change in its basal activity. This finding indicates the integrated function of AVP cells to both osmotic and volume stimuli. In the rats with hereditary hypothalamic diabetes insipidus, Brattleboro strain, expression of vasopressin dependent water channel, AQP-2, remained low even after vigorous water deprivation. The expression of AQP-2 is intensified in the rats with glucocorticoid deficiency and attenuated under the hyponatremic states resulting in the exaggeration and attenuation of urine concentration ability, respectively. Thus, in the action of AVP in the kidney, the regulation of AQP-2 takes a crucial role in forming a balanced circumstances of water homeostasis in the body.