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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 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., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Hydroelectrolytic imbalances, such as saline load (SL), trigger behavioral and neuroendocrine responses, such as thirst, hypophagia, vasopressin (AVP) and oxytocin (OT) release and hypothalamus–pituitary–adrenal (HPA) axis activation. To investigate the participation of the type-1 cannabinoid receptor (CB1R) in these homeostatic mechanisms,male adult Wistar rats were subjected to SL (0.3MNaCl) for four days. SL induced not only increases in the water intake and plasma levels of AVP, OT and corticosterone, as previously described, but also increases in CB1R expression in the lamina terminalis, which integrates sensory afferents, aswell as in the hypothalamus, the main integrative and effector area controlling hydroelectrolytic homeostasis. A more detailed analysis revealed that CB1R-positive terminals are in close apposition with not only axons but also dendrites and secretory granules of magnocellular neurons, particularly vasopressinergic cells. In satiated and euhydrated animals, the intracerebroventricular administration of the CB1R selective agonist ACEA (0.1 μg/5 μL) promoted hyperphagia, but this treatment did not reverse the hyperosmolality-induced hypophagia in the SL group. Furthermore, ACEA pretreatment potentiated water intake in the SL animals during rehydration as well as enhanced the corticosterone release and prevented the increase in AVP and OT secretion induced by SL. The same parameters were not changed by ACEA in the animals whose daily food intake was matched to that of the SL group (Pair-Fed). These data indicate that CB1Rs modulate the hydroelectrolytic balance independently of the food intake during sustained hyperosmolality and hypovolemia.

Endocannabinoids (ECBs) are ubiquitous lipophilic agents, and this characteristic is consistent with the wide range of homeostatic functions attributed to the ECB system. There is an increasing number of studies showing that the ECB system affects neurotransmission within the hypothalamic neurohypophyseal system. We provide an overview of the primary roles of ECBs in the modulation of neuroendocrine function and, specifically, in the control of hydromineral homeostasis. Accordingly, the general aspects of ECB-mediated signalling, as well as the specific contributions of the central component of the ECB system to the integration of behavioural and endocrine responses that control body fluid homeostasis, are discussed., (© 2014 British Society for Neuroendocrinology.)