During prolonged dehydration, body fluid homeostasis is challenged by extracellular fluid (ECF) hyperosmolality, which induce important functional changes in the hypothalamus, in parallel with other effector responses, such as the activation of the local renin-angiotensin system (RAS). Therefore, in the present study we investigated the role of sodium-driven ECF hyperosmolality on glial fibrillary acid protein (GFAP) immunoreactivity and protein expression, membrane capacitance, mRNA expression of RAS components and glutamate balance in cultured hypothalamic astrocytes. Our data show that hypothalamic astrocytes respond to increased ECF hyperosmolality with a similar decrease in GFAP expression and membrane capacitance, indicative of reduced cellular area. Hyperosmolality also downregulates the transcript levels of angiotensinogen and both angiotensin-converting enzymes, whereas upregulates type 1a angiotensin II receptor mRNA. Incubation with hypertonic solution also decreases the immunoreactivity to the membrane glutamate/aspartate transporter (GLAST) as well as tritiated-aspartate uptake by astrocytes. This latter effect is completely restored to basal levels when astrocytes previously exposed to hypertonicity are incubated under isotonic conditions. Together with a direct effect on two important local signaling systems (glutamate and RAS), these synaptic rearrangements driven by astrocytes may accomplish for a coordinated increase in the excitatory drive onto the hypothalamic neurosecretory system, ultimately culminating with increased AVP release in response to hyperosmolality.

在长时间的脱水过程中，体液稳态受到细胞外液（ECF）高渗的挑战，该渗透压会诱发下丘脑的重要功能变化，并伴随其他效应反应，例如激活局部肾素-血管紧张素系统（RAS）。因此，在本研究中，我们研究了钠驱动的ECF高渗性对培养的下丘脑星形胶质细胞中神经胶质纤维酸性蛋白（GFAP）免疫反应性和蛋白表达，膜电容，RAS组分的mRNA表达和谷氨酸平衡的作用。我们的数据显示，下丘脑星形胶质细胞对增加的ECF高渗性有反应，而GFAP表达和膜电容的降低类似，表明细胞面积减少。高渗性也下调血管紧张素原和两种血管紧张素转化酶的转录水平，而上调1a型血管紧张素II受体mRNA。与高渗溶液一起孵育还降低了对膜谷氨酸/天冬氨酸转运蛋白（GLAST）的免疫反应性以及星形胶质细胞对tri化天冬氨酸的摄取。当等渗条件下孵育先前暴露于高渗状态的星形胶质细胞时，后一种作用完全恢复到基础水平。与直接作用于两个重要的局部信号系统（谷氨酸和RAS）一起，这些由星形胶质细胞驱动的突触重排可实现对下丘脑神经分泌系统的兴奋性驱动力的协同增加，最终以对高渗性引起的AVP释放增加而达到高潮。