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Summary: 1. The present study provides the first in vivo evidence that the cannabinoid CB1 receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB1 receptor antagonist rimonabant (10 mg/Kg, p.o.), followed or not in 1 hour by dexamethasone (1 mg/Kg, i.p.). Extracellular volume expansion (EVE, 2 mL/ 100 g of body weight, i.v.) was performed 2 hours after dexamethasone or vehicle treatment using either isotonic (I‐EVE, 0.15 mol/L) or hypertonic (H‐EVE, 0.30 mol/L) NaCl solution. Five minutes after EVE, animals were decapitated and trunk blood was collected for all plasma measurements. 2. Rimonabant potentiated oxytocin (OT) secretion induced by H-EVE and completely reversed the inhibitory effects of dexamethasone in response to the same stimulus. These data suggest that glucocorticoid modulation of OT release is mediated by the CB1 receptor. 3. Although dexamethasone did not affect vasopressin (AVP) secretion induced by H-EVE, the administration of rimonabant potentiated AVP release in response to the same stimulus, supporting the hypothesis that the CB1 receptor regulates AVP secretion independently of glucocorticoid-mediated signalling. 4. Dexamethasone alone did not affect atrial natriuretic peptide (ANP) release stimulated by I-EVE or H-EVE. However, pretreatment with rimonabant potentiated ANP secretion induced by H-EVE, suggesting a possible role for the CB1 receptor in the control of peripheral factors that modulate cardiovascular function. 5. Rimonabant also reversed the inhibitory effects of dexamethasone on H-EVE-induced corticosterone secretion, reinforcing the hypothesis that the CB1 receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic–pituitary–adrenal axis. 6. Collectively, the results of the present study indicate that the CB1 receptor modulates neurohypophyseal hormone secretion and systemic factors, such as corticosterone and ANP, thus participating in homeostatic responses to altered extracellular volume and plasma tonicity. [ABSTRACT FROM AUTHOR]

The renin angiotensin system (RAS) has been studied for its effects on various neurological disorders. The identification of functional receptors for Ang-(1-7) and Ang II peptides in astrocytes highlights the physiological modulation and the important role of these cells in the central nervous system. The present study aims to understand the role of RAS peptides, particularly Ang-(1-7) and Ang II, in the secretion of trophic factors by astrocytes and their effects on hippocampal neurons. We used primary cultures of astrocytes and neurons from the hippocampus of either sex neonate of Wistar strain rats. In the present study, we demonstrated that the treatment of astrocytes with Ang-(1-7) acts on the modulation of these cells, inducing reactive astrogliosis, identified through the increase in the expression of GFAP. Furthermore, we obtained a conditioned medium from astrocytes treated with Ang-(1-7), which in addition to promoting the secretion of neurotrophic factors essential for neuronal-glial interactions that are fundamental for neuritogenesis and neuronal survival, showed a neuroprotective effect against glutamatergic excitotoxicity. In turn, Ang II does not exhibit the same effects on astrocyte modulation, exacerbating deleterious effects on brain RAS. Neuron-astrocyte interactions have been shown to be an integral part of the central effects mediated by RAS, and this study has significantly contributed to the understanding of the biochemical mechanisms involved in the functioning of this system., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the present study, we investigated whether curcumin administration would interfere with the main renal features of l-NAME-induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l-NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l-NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l-NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP-2 activity, as well as MMP-9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP-2 activity, and reduced MMP-2, MMP-9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP-2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l-NAME-induced hypertension and renal glomerular alterations, inhibited MMP-2 and MMP-9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension-induced renal outcomes., (© 2024 John Wiley & Sons Ltd.)

Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nicotine has been used during pregnancy and lactation as a tobacco harm reduction strategy. However, it is unclear whether nicotine exposure during a critical development period negatively impacts stress responses in adulthood. This study investigated how nicotine, administered via breastfeeding, affects the brain-derived neurotrophic factor (BDNF), synaptic proteins levels, and anxiety-like behavior in adult female mice subjected to stress. Female Swiss mice were exposed to saline or nicotine (8 mg/kg/day) through breastfeeding between their fourth and 17th postnatal days (P) via implanted osmotic mini pumps. The unpredictable chronic mild stress (UCMS) protocol was performed during their adulthood (P65) for 10 consecutive days, followed by the elevated plus maze (EPM) test 1 day after the protocol. Animals were euthanized and their blood, collected for plasma corticosterone measurements and their brain structures, dissected for BDNF and synaptic proteins analyses. We found no significant differences in corticosterone levels between groups (Saline/Non-stress, Nicotine/Non-stress, Saline/Stress, and Nicotine/Stress). The UCMS protocol hindered weight gain. Mice exposed to nicotine through breastfeeding with or without the UCMS protocol in adulthood showed higher grooming and head dipping frequency; decreased BDNF levels in cerebellum and striatum; increased postsynaptic density protein 95 (PSD-95), synapsin I, and synaptophysin levels in cerebellum; and decreased PSD-95 and synapsin I levels in brainstem. Our results indicate that nicotine exposure through breastfeeding leads to long-lasting behavioral effects and synaptic protein changes, most of which were independent of the UCMS protocol, even after a long nicotine-free period, highlighting the importance of further studies on nicotine exposure during development., (© 2022 International Society for Developmental Neuroscience.)

The gaseous modulator hydrogen sulfide (H 2 S) is synthesized, among other routes, by the action of cystathionine-γ-lyase (CSE) and importantly participates in body fluid homeostasis. Therefore, the present study aimed to evaluate the participation of H 2 S in behavioral, renal and neuroendocrine homeostatic responses triggered by the acute consumption of a high Na + diet. After habituation, adult male Wistar rats were randomly distributed and maintained for seven days on a control [CD (0.27% of Na + )] or hypersodic diet [HD (0.81% of Na + )]. CD and HD-fed animals were treated with DL-Propargylglycine (PAG, 25 mg/kg/day, ip) or vehicle (0.9% NaCl in equivalent volume) for the same period. At the end of the experiment, animals were euthanized for blood and tissue collection. We demonstrated that a short-term increase in dietary Na + intake, in values that mimic the variations in human consumption (two times the recommended) significantly modified hydroelectrolytic homeostasis, with repercussions in the hypothalamic-neurohypophysial system and hypothalamic-pituitary-adrenal axis function. These findings were accompanied by the development of a clear inflammatory response in renal tubular cells and microvascular components. On the other hand, the inhibition of the endogenous production of H 2 S by CSE provided by PAG treatment prevented the inflammation induced by HD. In the kidney, PAG treatment induced the overexpression of inducible nitric oxide synthase in animals fed with HD. Taken together, these data suggest, therefore, that HD-induced H 2 S production plays an important proinflammatory role in the kidney, apparently counter regulating nitric oxide actions in renal tissue.

Zika virus (ZIKV) is a mosquito-borne Flavivirus structurally and antigenically related to Dengue virus (DENV). Zika virus has been associated with congenital anomalies and most ZIKV outbreaks have occurred in endemic areas of DENV. The present study investigated the effects of prior DENV serotype 1 (DENV1) immunity in immunocompetent female Swiss mice on gestational ZIKV infection in offspring. Physical/reflex development, locomotor activity, anxiety, visual acuity, and brain-derived neurotrophic factor (BDNF) levels were evaluated in offspring during infancy and adolescence. Anti-DENV1 and anti-ZIKV antibodies were detected in sera of the progenitors, whereas no ZIKV genomes were detected in the offspring brain. Pups from dams with only DENV1 immunity presented alterations of physical/reflex development. Pups from all infected dams exhibited time-related impairments in locomotor activity and anxiolytic-like behavior. Offspring from DENV/ZIKV-infected dams exhibited impairments in visual acuity during infancy but not during adolescence, which was consistent with morphometric analysis of the optic nerve. Pups from DENV1-, ZIKV-, and DENV/ZIKV-infected dams exhibited a decrease in BDNF levels during infancy and an increase during adolescence in distinct brain regions. In summary, we found no influence of prior DENV1 immunity on gestational ZIKV infection in offspring, with the exception of alterations of early visual parameters, and an increase in BDNF levels in the hippocampus during adolescence., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We examined the effect of the NFκB inhibitor pyrrolidine-1-carbodithioic acid (PDTC) on inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2) activity, and oxidative and inflammatory kidney damage in alloxan-induced diabetes. Two weeks after diabetes induction (alloxan-130 mg/kg), control and diabetic rats received PDTC (100 mg/kg) or vehicle for 8 weeks. Body weight, glycemia, urea, and creatinine were measured. Kidney changes were measured in hematoxylin/eosin sections and ED1 by immunohistochemistry. Kidney thiobarbituric acid reactive substances (TBARS), superoxide anion (O2-), and nitrate/nitrite (NOx) levels, and catalase and superoxide dismutase (SOD) activities were analyzed. Also, kidney nox4 and iNOS expression, and NFkB nuclear translocation were measured by western blot, and MMP-2 by zymography. Glycemia and urea increased in alloxan rats, which were not modified by PDTC treatment. However, PDTC attenuated kidney structural alterations and macrophage infiltration in diabetic rats. While diabetes increased both TBARS and O 2 - levels, PDTC treatment reduced TBARS in diabetic and O 2 - in control kidneys. A decrease in NO x levels was found in diabetic kidneys, which was prevented by PDTC. Diabetes reduced catalase activity, and PDTC increased catalase and SOD activities in both control and diabetic kidneys. PDTC treatment reduced MMP-2 activity and iNOS and p65 NFκB nuclear expression found increased in diabetic kidneys. Our results show that the NFκB inhibitor PDTC reduces renal damage through reduction of Nox4, iNOS, macrophages, and MMP-2 in the alloxan-induced diabetic model. These findings suggest that PDTC inhibits alloxan kidney damage via antioxidative and anti-inflammatory mechanisms.

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.)

Aims and Objectives: To compare the efficacy of Chinese and French ear acupuncture in people with chronic back pain., Background: Chronic back pain is a common public health problem worldwide. An intervention for this condition is ear acupuncture. Several approaches are used for ear acupuncture, particularly the Chinese and French guidelines., Methods: An open, randomised and controlled clinical trial, followed the recommendations of the CONSORT Checklist. One hundred and eleven people were selected and randomised into three groups: Chinese ear acupuncture, French ear acupuncture and Control. Evaluations were performed before the first intervention session (initial), 1 week after the fifth session (final) and after a fifteen-day follow-up period (follow-up), using the Brief Pain Inventory, Rolland Morris Disability Questionnaire, and a thermal imaging camera. For data analysis, the Generalized Estimating Equation Model was applied, with significance level set at 5%., Results: Pain severity was significantly decreased by Chinese ear acupuncture throughout intervention period. Both types of ear acupuncture affected pain interference with daily activities. However, in the comparison between initial and final evaluations, only Chinese ear acupuncture produced statistically significant results. A reduction in physical disability was observed in both ear acupuncture-treated groups during the intervention period and, although Chinese ear acupuncture failed to induce significant changes in tissular temperature at individual time points, a significant increase in cutaneous temperature was detected after the follow-up period in the dorsal region of individuals treated with Chinese ear acupuncture. Importantly, at this time point, the mean difference between Chinese and French ear acupuncture revealed a more benefic effect of Chinese procedure on this parameter., Conclusions: The individualised treatment based on the Chinese precepts showed, in an overall evaluation, better results for management of chronic back pain in the present study., Relevance to Clinical Practice: Ear acupuncture can be implemented in the nurse's clinical practice to assist the treatment of people with chronic back pain., (© 2019 John Wiley & Sons Ltd.)

Adrenalectomy (ADX) induces hypophagia and glucocorticoids counter-regulate the peripheral metabolic effects of insulin. This study evaluated the effects of ADX on ICV (lateral ventricle) injection of insulin-induced changes on food intake, mRNA expression of hypothalamic neuropeptides (insulin receptor (InsR), proopiomelanocortin, cocaine and amphetamine-regulated transcript (Cart), agouti-related protein, neuropeptide Y (Npy) in the arcuate nucleus of the hypothalamus (ARC), corticotrophin-releasing factor in the paraventricular nucleus of the hypothalamus) and hypothalamic protein content of insulin signaling-related molecules (insulin receptor substrate (IRS) 1, protein kinase B (AKT), extracellular-signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), protein tyrosine phosphatase-1B (PTP1B) and T cell protein tyrosine phosphatase (TCPTP)) Compared with sham animals, ADX increased the hypothalamic content of pJNK/JNK, PTP1B and TCPTP, as well as decreased mRNA expression of InsR, and corticosterone (B) treatment reversed these effects. Insulin central injection enhanced hypothalamic content of pAKT/AKT and Cart mRNA expression, decreased Npy mRNA expression and food intake only in sham rats, without effects in ADX and ADX + B rats. Insulin did not alter the hypothalamic phosphorylation of IRS1 and ERK1/2 in the three experimental groups. These data demonstrate that ADX reduces the expression of InsR and increases insulin counter-regulators in the hypothalamus, as well as ADX abolishes hypophagia, activation of hypothalamic AKT pathway and changes in Cart and Npy mRNA expression in the ARC induced by insulin. Thus, the higher levels of insulin counter-regulatory proteins and lower expression of InsR in the hypothalamus are likely to underlie impaired insulin-induced hypophagia and responses in the hypothalamus after ADX.

Objective: To evaluate the effects of auricular acupuncture on pain intensity, its impact on daily activities, the relief provided by the intervention, and the pain threshold in people with back musculoskeletal disorders., Methods: Randomized clinical trial carried out with people randomly allocated into three groups: treatment, placebo, and control. Evaluations were performed using the Brief Pain Inventory and a digital algometer before (initial) and after (final) the treatment and after a 15-day follow-up period., Results: The sample was 110 people. There was a decrease in pain intensity in the treatment and placebo groups as revealed by the comparison between the initial and final evaluations (p<0.05), and in the treatment group in the comparison between the initial and follow-up evaluations (p<0.05). A decreased impact of pain on daily activities in the treatment and placebo groups over time was found (p<0.05). At the final evaluation, the impact of pain was lower in the treatment group (p<0.05). Auricular acupuncture did not increase the pain threshold., Conclusion: Auricular acupuncture presented positive effects by reducing the chronic pain intensity and its impact on daily activities in people with back musculoskeletal disorders. Brazilian Clinical Trials Registry: RBR-5X69X2.

Glucocorticoids (GCs) are used for acute respiratory distress syndrome (ARDS) to improve or prevent lung injury. The mechanisms underlying the effects of GCs involve inadequate GC-receptor (GR)-mediated downregulation of pro-inflammatory factors despite elevated levels of cortisol. Within this context, knowledge of the transcriptional pattern of the GR gene in response to variations in physiological parameters may shed light on this issue. We addressed this problem by measuring plasmatic corticosterone (CCT) levels and assessing GR expression at transcript and protein levels in rats with caecal ligation and puncture (CLP)-induced ARDS-like syndrome treated with dexamethasone and metyrapone. Seventy male rats were randomized into three main groups: Naïve (any treatment), Sham (caecum-exposed) and CLP. CLP animals were divided into three groups according to pretreatments performed before surgery: CLP sal (0.9% NaCl ip), CLP metyrapone (50 mg.kg-1 ip) and CLP dexamethasone (0.5 mg.kg-1 ip). Our results showed that CLP sal promotes elevation in CCT levels, which are significantly reduced with metyrapone to levels comparable to untreated animals when dexamethasone is used. In this hormonal milieu, the GR gene transcript levels of both variants, GRα and GRβ, are produced in comparable levels and in response to caecum-exposing surgery. Nonetheless, the expression of the GRα variant demonstrated positive sensitivity to variations in CCT levels and was downregulated in animals treated with dexamethasone. Moreover, nuclear translocation of GR protein decreased with high levels of plasma CCT and higher GR translocation was found in animals with moderate CCT levels; in either case, the process seemed to be positively associated with the CLP procedure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: to assess the action of ear acupuncture on disability and tissue temperature in people with chronic pain in the spinal column., Method: a clinical trial with a sample of 110 people, randomized into three groups: Treatment, Placebo and Control. The assessment instruments were the Rolland Morris Disability Questionnaire (RMDQ) and a thermographic camera, administered before the first treatment session, one week after and 15 days after (follow-up) the fifth session of ear acupuncture. In the analysis of the data, the Kruskal Wallis, Student-Newman Keuls and Wilcoxon tests were applied., Results: there was a significant reduction in disability in the Treatment and Placebo groups between the initial and final assessments (p<0.05) and between the initial assessments and follow-up (p<0.05). In the final assessment, the Treatment group presented improvement of disability when compared with the Placebo and Control groups (p<0.05). There was an increase in mean tissue temperature of the dorsal region between the initial and follow-up assessments in Treatment and Control groups (p<0.05), and between the final assessments and follow-up in the Treatment and Placebo groups (p<0.05)., Conclusion: ear acupuncture was efficacious in reducing disability and increasing tissue temperature in people with chronic pain in the spinal column. Brazilian Register of Clinical Trials (RBR-5X69X2).

It is known that circulating angiotensin II (ANG-II) acts on the circumventricular organs (CVOs), which partially lack a normal blood-brain barrier, to stimulate pressor responses, vasopressin (AVP), and oxytocin (OT) secretion, as well as sodium and water intake. Although ANG-II type 1 receptors (AT1 R ) are expressed in neurons and astrocytes, the involvement of CVOs glial cells in the neuroendocrine, cardiovascular and behavioral responses induced by central ANG II remains to be further elucidated. To address this question, we performed a set of experiments combining in vitro studies in primary hypothalamic astrocyte cells (HACc) and in vivo intracerebroventricular (icv) microinjections into the lateral ventricle of awake rats. Our results showed that ANG-II decreased glutamate uptake in HACc. In addition, in vivo studies showed that fluorocitrate (FCt), a reversible glial inhibitor, increased OT secretion and mean arterial pressure (MAP) and decreased breathing at rest. Furthermore, previous FCt decreased AVP secretion and sodium intake induced by central ANG-II. Together, our findings support that CVOs glial cells are important in mediating neuroendocrine and cardiorespiratory functions, as well as central ANG-II-induced AVP release and salt-intake behavior in awake rats. In the light of our in vitro studies, we propose that these mechanisms are, at least in part, by ANG-II-induced astrocyte mediate reduction in glutamate extracellular clearance.

Androgen deficiency is strongly associated with erectile dysfunction (ED). Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries (IPAs); however, no study has evaluated the effects of androgen deprivation on IPA's function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation (EFS)-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 (Thr180/Tyr182) phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.

Fluoxetine, a serotonin reuptake inhibitor (SSRI), has other effects in addition to blocking serotonin reuptake, including changes in the vasomotor tone. Whereas many studies focused on the acute effects of fluoxetine in the vasculature, its chronic effects are still limited. In the present study, we tested the hypothesis that chronic fluoxetine treatment modulates adrenergic vascular responses by interfering with post- and pre-synaptic mechanisms. Wistar rats were treated with vehicle (water) or chronic fluoxetine (10mg/kg/day) for 21 days. Blood pressure (BP) and heart rate were measured. Vascular reactivity was evaluated in perfused mesenteric arterial beds (MAB) and in mesenteric resistance arteries. Protein expression by western blot analysis or immunohistochemistry, β-arrestin recruitment by BRET and calcium influx by FLIPR assay. Fluoxetine treatment decreased phenylephrine (PE)-induced, but not electrical-field stimulation (EFS)-induced vasoconstriction. Fluoxetine-treated rats exhibited increased KCl-induced vasoconstriction, which was abolished by prazosin. Desipramine, an inhibitor of norepinephrine (NA) reuptake, increased EFS-induced vasoconstrictor response in vehicle-treated, but not in fluoxetine-treated rats. Chronic treatment did not alter vascular expression of α 1 adrenoceptor, phosphorylation of PKCα or ERK 1/2 and RhoA. On the other hand, vascular contractions to calcium (Ca 2+ ) as well as Ca 2+ influx in mesenteric arteries were increased, while intracellular Ca 2+ storage was decreased by the chronic treatment with fluoxetine. In vitro, fluoxetine decreased vascular contractions to PE, EFS and Ca 2+ , but did not change β-arrestin activity. In conclusion, chronic treatment with fluoxetine decreases sympathetic-mediated vascular responses by mechanisms that involve inhibition of NA release/reuptake and decreased Ca 2+ stores., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Excessive sodium (Na + ) intake in modern society has been associated with several chronic disorders such as hypertension. Several studies suggest that early life events can program physiological systems and lead to functional changes in adulthood. Therefore, we investigated behavioral and neuroendocrine responses under basal conditions and after 48 h of water deprivation in adult (60-day-old Wistar rats) male, Wistar rats originating from dams were offered only water or 0.15 mol/L NaCl during pregnancy and lactation. Early life salt exposure induced kidney damage, as shown by a higher number of ED-1 positive cells (macrophages/monocytes), increased daily urinary volume and Na + excretion, blunted basal water intake and plasma oxytocin levels, and increased plasma corticosterone secretion. When challenged with water deprivation, animals exposed to 0.15 mol/L NaCl during early life showed impaired water intake, reduced salt preference ratio, and vasopressin (AVP) secretion. In summary, our data demonstrate that the perinatal exposure to excessive Na + intake can induce kidney injury in adult offspring and significantly affect the key mechanisms regulating water balance, fluid intake, and AVP release in response to water deprivation. Collectively, these novel results highlight the impact of perinatal programming on the homeostatic mechanisms regulating fluid and electrolyte balance during exposure to an environmental stress (i.e. dehydration) in later life., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

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.

The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 h of water deprivation, which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis. The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of water-deprived (WD) rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses. Although the administration of ACEA or AM251 did not produce any effects on WD-induced arginine vasopressin (AVP) secretion, oxytocin (OXT) plasma concentrations were significantly decreased in WD rats treated with ACEA. At the genomic level, ACEA significantly decreased AVP and OXT mRNA expression in the hypothalamus of WD rats, whereas AM251 potentiated both basal and WD-induced stimulatory effects on the transcription of AVP and OXT genes. In addition, we showed that water deprivation alone upregulated proopiomelanocortin, Agouti-related peptide, melanin-concentrating hormone, and orexin A mRNA levels in the hypothalamus, and that CB1Rs regulate main central peptidergic pathways controlling food intake, being that most of these effects were also significantly influenced by the hydration status. In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation., (Copyright © 2015 the American Physiological Society.)

Adrenalectomy (ADX)-induced hypophagia is associated with increased activation of corticotrophin-releasing factor (CRF) and oxytocin (OT) neurons in the paraventricular nucleus of the hypothalamus (PVN) after refeeding. CRF2- and OT-receptor antagonists abolish the hypophagia and the augmented activation of the nucleus of the solitary tract neurons induced by feeding after ADX. In addition, OT-receptor antagonist reversed CRF-induced anorexia. We evaluated the effect of intracerebroventricular pretreatment with CRF2-receptor antagonist, antisauvagine-30 (AS30), on the activation of OT neurons of the PVN in response to refeeding of sham, adrenalectomized (ADX) and ADX rats replaced with corticosterone (ADX+B). In vehicle-pretreated animals, refeeding increased the number of Fos+OT double labeled neurons in the posterior parvocellular subdivision of the PVN (PaPo) of sham, ADX and ADX+B animals, with higher Fos expression and OT neuronal activation in the ADX group. AS30 reversed refeeding-induced increased activation of OT and non-OT neurons in the PaPo in the ADX group. In the medial parvocellular subdivision of the PVN (PaMP) of vehicle-pretreated animals, the number of Fos- and Fos+OT-immunoreactive neurons was increased after refeeding in ADX group. AS30 in the ADX group attenuated the enhanced Fos expression but not the number of Fos+OT double labeled neurons in the PaMP. In conclusion, CRF2-receptor antagonist reverses the increased activation of OT neurons in the PaPo induced by feeding in ADX animals, suggesting that OT neurons might be downstream mediators of CRF effects on satiety-related responses after ADX., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Since the crucial evolutionary change from an aqueous to a terrestrial environment, all living organisms address the primordial task of equilibrating the ingestion/production of water and electrolytes (primarily sodium) with their excretion. In mammals, the final route for the excretion of these elements is mainly through the kidneys, which can eliminate concentrated or diluted urine according to the requirements. Despite their primary role in homeostasis, the kidneys are not able to recover water and solutes lost through other systems. Therefore, the selective stimulation or inhibition of motivational and locomotor behavior becomes essential to initiate the search and acquisition of water and/or sodium from the environment. Indeed, imbalances affecting the osmolality and volume of body fluids are dramatic challenges to the maintenance of hydromineral homeostasis. In addition to behavioral changes, which are integrated in the central nervous system, most of the systemic responses recruited to restore hydroelectrolytic balance are accomplished by coordinated actions of the cardiovascular, autonomic and endocrine systems, which determine the appropriate renal responses. The activation of sequential and redundant mechanisms (involving local and systemic factors) produces accurate and self-limited effector responses. From a physiological point of view, understanding the mechanisms underlying water and sodium balance is intriguing and of great interest for the biomedical sciences. Therefore, the present review will address the biophysical, evolutionary and historical perspectives concerning the integrative neuroendocrine control of hydromineral balance, focusing on the major neural and endocrine systems implicated in the control of water and sodium balance., (© 2015 American Physiological Society.)

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are gaseous molecules produced by the brain. Within the hypothalamus, gaseous molecules have been highlighted as autocrine and paracrine factors regulating endocrine function. Therefore, in the present review, we briefly discuss the main findings linking NO, CO, and H2S to the control of body fluid homeostasis at the hypothalamic level, with particular emphasis on the regulation of neurohypophyseal system output., (©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.)

The aim of the present work was to establish a time-course correlation between vascular and autonomic changes that contribute to the development of hypertension during ethanol ingestion in rats. For this, male Wistar rats were subjected to the intake of increasing ethanol concentrations in their drinking water during four weeks. Ethanol effects were investigated at the end of each week. Mild hypertension was already observed at the first week of treatment, and a progressive blood pressure increase was observed along the evaluation period. Increased pressor response to phenylephrine was observed from first to fourth week. α1-Adrenoceptor protein in the mesenteric bed was enhanced at the first week, whereas β2-adrenoceptor protein in the aorta was reduced after the second week. In the third week, ethanol intake facilitated the depressor response to sodium nitroprusside, whereas in the fourth week it reduced nitrate content in aorta and increased it plasma. The bradycardic component of the baroreflex was impaired, whereas baroreflex tachycardia was enhanced at the third and fourth weeks. AT1A receptor and C-type natriuretic peptide (CNP) mRNAs in the nucleus tractus solitarius were increased at the fourth week. These findings suggest that increased vascular responsiveness to vasoconstrictor agents is possibly a link factor in the development and maintenance of the progressive hypertension induced by ethanol consumption. Additionally, baroreflex changes are possibly mediated by alterations in angiotensinergic mechanisms and CNP content within the brainstem, which contribute to maintaining the hypertensive state in later phases of ethanol ingestion. Facilitated vascular responsiveness to nitric oxide seems to counteract ethanol-induced hypertension., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.)

It has been shown that glucocorticoids can modulate oxytocin (OT) secretion and disrupt maternal behaviour. Because the CB1 receptor (CB1R) has been implicated in some rapid glucocorticoid-induced actions, the present study aimed to evaluate the possible involvement of CB1Rs in maternal behaviour and neuronal activation during lactation. For this purpose, lactating female rats were pre-treated with dexamethasone (DEX) or saline, followed by treatment with AM251, a CB1R antagonist, or vehicle 90 min later. All of the experiments were performed 30 min after the administration of AM251 or vehicle. To evaluate maternal behaviour, the pups were returned to their home cages to the side of the cage opposite the previous nest after 12 h of separation and were filmed for the next 30 min. Aggressive behaviour was evaluated for 10 min following the placement of a male rat in the home cage. For the evaluation of behavioural performance, lactating rats were subjected to a T-maze and open-field tests. The amount of weight gained by the pups was evaluated 15 min after the onset of suckling to determine the amount of milk that they had obtained from the dam. In the central nervous system of lactating rats, c-Fos-positive nuclei were counted in the medial preoptic area, in both the ventral (v) and dorsal (d) parts of the median preoptic nucleus and in the bed nucleus of the stria terminalis (BNST). The number of neurons that were double-labelled for c-Fos/OT was counted in the medial magnocellular subdivision of the paraventricular nucleus, in the periventricular hypothalamic nucleus and in the supraoptic nucleus of the lactating rats. The results show that DEX had the following effects: (1) decreased the amount time the dam spent licking the pups, the amount of time the dam spent in an arched-nursing position and full maternal behaviour; (2) increased the latency to the first attack and decreased front attacks; (3) increased anxiety-like behaviour; and (4) decreased weight gain in the pups. In addition, DEX decreased neuronal activation in all of the investigated hypothalamic and forebrain areas. AM251 administration reversed these parameters, indicating that the behavioural effects and neuronal responses produced by DEX in lactating rats are likely to be mediated by CB1Rs.

Unlabelled: Ethanol (ETOH) consumption has been associated with endocrine and autonomic changes, including the development of hypertension. However, the sequence of pathophysiological events underlying the emergence of this effect is poorly understood., Aims: This study aimed to establish a time-course correlation between neuroendocrine and cardiovascular changes contributing to the development of hypertension following ETOH consumption., Methods: Male adult Wistar rats were subjected to the intake of increasing ETOH concentrations in their drinking water (first week: 5%, second week: 10%, third and fourth weeks: 20% v/v)., Results: ETOH consumption decreased plasma and urinary volumes, as well as body weight and fluid intake. Furthermore, plasma osmolality, plasma sodium and urinary osmolality were elevated in the ETOH-treated rats. ETOH intake also induced a progressive increase in the mean arterial pressure (MAP), without affecting heart rate. Initially, this increase in MAP was correlated with increased plasma concentrations of adrenaline and noradrenaline. After the second week of ETOH treatment, plasma catecholamines returned to basal levels, and incremental increases were observed in plasma concentrations of vasopressin (AVP) and angiotensin II (ANG II). Conversely, plasma oxytocin, atrial natriuretic peptide, prolactin and the hypothalamus-pituitary-adrenal axis components were not significantly altered by ETOH., Conclusions: Taken together, these results suggest that increased sympathetic activity may contribute to the early increase in MAP observed in ETOH-treated rats. However, the maintenance of this effect may be predominantly regulated by the long-term increase in the secretion of other circulating factors, such as AVP and ANG II, the secretion of both hormones being stimulated by the ETOH-induced dehydration.

Several forebrain and brainstem neurochemical circuitries interact with peripheral neural and humoral signals to collaboratively maintain both the volume and osmolality of extracellular fluids. Although much progress has been made over the past decades in the understanding of complex mechanisms underlying neuroendocrine control of hydromineral homeostasis, several issues still remain to be clarified. The use of techniques such as molecular biology, neuronal tracing, electrophysiology, immunohistochemistry, and microinfusions has significantly improved our ability to identify neuronal phenotypes and their signals, including those related to neuron-glia interactions. Accordingly, neurons have been shown to produce and release a large number of chemical mediators (neurotransmitters, neurohormones and neuromodulators) into the interstitial space, which include not only classic neurotransmitters, such as acetylcholine, amines (noradrenaline, serotonin) and amino acids (glutamate, GABA), but also gaseous (nitric oxide, carbon monoxide and hydrogen sulfide) and lipid-derived (endocannabinoids) mediators. This efferent response, initiated within the neuronal environment, recruits several peripheral effectors, such as hormones (glucocorticoids, angiotensin II, estrogen), which in turn modulate central nervous system responsiveness to systemic challenges. Therefore, in this review, we shall evaluate in an integrated manner the physiological control of body fluid homeostasis from the molecular aspects to the systemic and integrated responses.

Several studies suggest that hypothalamic cocaine- and amphetamine-regulated transcript (CART) may interact with the hypothalamic-pituitary-adrenal (HPA) axis in the control of neuroendocrine function and may also participate in cardiovascular regulation. Therefore, this study aimed to evaluate, in experimental models of isotonic (I-EVE) and hypertonic (H-EVE) extracellular volume expansion and water deprivation (WD), the activation of CART- and corticotrophin releasing factor (CRF)-immunoreactive neurons, as well as the relative expression of CART and CRF mRNAs in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. Both H-EVE (0.30M NaCl, 2mL/100g of body weight, in 1 minute) and 24 hours of WD significantly increased plasma sodium concentrations, producing, respectively, either an increase or a decrease in extracellular volume. I-EVE (0.15M NaCl, 2mL/100g of body weight, in 1 minute) evoked a significant increase in the circulating volume accompanied by unaltered plasma concentrations of sodium. CART-expressing neurons of both magnocellular and parvocellular hypothalamic divisions were activated to produce Fos in response to H-EVE but not in response to I-EVE. Furthermore, increased expression of CART mRNA was found in the PVN of H-EVE but not I-EVE rats. These data show for the first time that EVE not only activates hypothalamic CRF neurons but also increases CRF mRNA expression in the PVN. In contrast, WD increases the number of CART-immunoreactive neurons activated to produce Fos in the PVN and SON but does not change the number of neurons double labeled for Fos and CRF or expression of CRF mRNA in the PVN. These findings provided new insights into the participation of CART in diverse processes within the PVN and SON, including its possible involvement in activation of the HPA axis and cardiovascular regulation in response to changes in extracellular volume and osmolality., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

The endocannabinoid system includes important signaling molecules that are involved in several homeostatic and neuroendocrine functions. In the present study, we evaluated the effects of the type 1 cannabinoid (CB(1)) receptor antagonist, rimonabant (10 mg/kg, p.o.), on hormone secretion, neuronal activation and mRNA expression in the hypothalamus following isotonic (I-) or hypertonic (H-) extracellular volume expansion (EVE). The total nitrate content in the PVN and SON was also assessed under the same experimental conditions. Our results showed that OT and AVP plasma concentrations were increased in response to H-EVE, while decreased AVP levels were found following I-EVE. Accordingly, both I- and H-EVE stimulated oxytocinergic neuronal activation, as evidenced by the increased number of c-Fos/OT double labeled neurons in the hypothalamus. The vasopressinergic cells of the PVN and SON, however, were only activated in response to H-EVE. Furthermore, increased amounts of both AVP and OT mRNAs were found in the hypothalamus following EVE. Pretreatment with rimonabant significantly potentiated hormone secretion and also vasopressinergic and oxytocinergic neuronal activation induced by EVE, although decreased AVP and OT mRNA expression was found in the hypothalami of rimonabant pretreated groups. In addition, the nitrate content in the PVN and SON was not altered in response to EVE or rimonabant pretreatment. Taken together, these results suggest that the CB(1) receptor may modulate several events that contribute to the development of appropriate responses to increased fluid volume and osmolality., (Copyright 2010 Elsevier Inc. All rights reserved.)

Glucocorticoids have major effects on food intake, demonstrated by the decrease of food intake following adrenalectomy. Satiety signals are relayed to the nucleus of the solitary tract (NTS), which has reciprocal projections with the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. We evaluated the effects of glucocorticoids on the activation of hypothalamic and NTS neurons induced by food intake in rats subjected to adrenalectomy (ADX) or sham surgery 7 days before the experiments. One-half of ADX animals received corticosterone (ADX+B) in the drinking water (B: 25 mg/l). Fos/tyrosine hydroxylase (TH), Fos/corticotrophin-releasing factor (CRF) and Fos immunoreactivity were assessed in the NTS, PVN, and ARC, respectively. Food intake and body weight were reduced in the ADX group compared with sham and ADX+B groups. Fos and Fos/TH in the NTS, Fos, and Fos/CRF immunoreactive neurons in the PVN and Fos in the ARC were increased after refeeding, with higher number in the ADX group, compared with sham and ADX+B groups. CCK administration showed no hypophagic effect on ADX group despite a similar increase of Fos/TH immunoreactive neurons in the NTS compared with sham and ADX+B groups, suggesting that CCK alone cannot further increase the anorexigenic effect induced by glucocorticoid deficiency. The present data indicate that glucocorticoid withdrawal reduced food intake, which was associated with higher activation of ARC, CRF neurons of the PVN, and catecholaminergic neurons of the NTS. In the absence of glucocorticoids, satiety signals elicited during a meal lead to an augmented activation of brain stem and hypothalamic pathways.

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor kappaB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.

The present study evaluated the involvement of glucocorticoid in the activation of vasopressinergic and oxytocinergic neurons of hypothalamic nuclei and plasma levels of vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP) and corticosterone (CORT) in response to both isotonic and hypertonic blood volume expansion (BVE). Rats were subjected to isotonic (0.15 M NaCl, 2 ml/100 g b.w., i.v.) or hypertonic (0.30 M NaCl, 2 ml/100 g b.w., i.v.) BVE with or without pre-treatment with dexamethasone (1 mg/kg, i.p.). Results showed that isotonic BVE increased OT, ANP and CORT, and decreased AVP plasma levels. On the other hand, hypertonic BVE enhanced AVP, ANP, OT, and CORT plasma concentrations. Both hypertonic and isotonic BVE induced an increase in the number of Fos-OT double-labeled magnocellular neurons in the PVN and SON. Pre-treatment with dexamethasone reduced OT secretion, as well as Fos-OT immunoreactive neurons in response to both isotonic and hypertonic BVE. We also observed that dexamethasone pre-treatment had no effect on AVP secretion in response to hypertonic BVE, although this effect was associated with a blockade of Fos expression in the vasopressinergic magnocellular neurons in the PVN and SON. In conclusion, these data suggest that, not only the rapid OT release from storages, but also the oxytocinergic cellular activation induced by BVE are modulated by glucocorticoids. However, this pattern of response was not observed for AVP cells, suggesting that dexamethasone is not likely to influence rapid release of AVP but seems to modulate the activation of these neurons in response to hypertonic BVE.

The regulation of fluid and electrolyte homeostasis involves the participation of several neuropeptides and hormones that utilize hypothalamic cholinergic, alpha-adrenergic and angiotensinergic neurotransmitters and pathways. Additionally, it has been suggested that hypothalamus-pituitary-adrenal axis activity modulates hormonal responses to blood volume expansion. In the present study, we evaluated the effect of dexamethasone on atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) responses to i.c.v. microinjections of 0.15 M and 0.30 M NaCl, angiotensin-II (ANG-II) and carbachol. We also evaluated the Fos protein immunoreactivity in the median preoptic (MnPO), paraventricular (PVN) and supraoptic (SON) nuclei. Male Wistar rats received an i.p. injection of dexamethasone (1 mg/kg) or vehicle (0.15 M NaCl) 2 h before the i.c.v. microinjections. Blood samples for plasma ANP, OT, AVP and corticosterone determinations were collected at 5 and 20 min after stimulus. Another set of rats was perfused 120 min after stimulation. A significant increase in plasma ANP, OT, AVP and corticosterone levels was observed at 5 and 20 min after each central stimulation compared with isotonic saline-injected group. Pre-treatment with dexamethasone decreased plasma corticosterone and OT levels, with no changes in the AVP secretion. On the other hand, dexamethasone induced a significant increase in plasma ANP levels. A significant increase in the number of Fos immunoreactive neurons was observed in the MnPO, PVN and SON after i.c.v. stimulations. Pre-treatment with dexamethasone induced a significant decrease in Fos immunoreactivity in these nuclei compared with the vehicle. These results indicate that central osmotic, cholinergic, and angiotensinergic stimuli activate MnPO, PVN and SON, with a subsequent OT, AVP, and ANP release. The present data also suggest that these responses are modulated by glucocorticoids.

This study evaluated the role of nitric oxide (NO) in vasopressin (AVP) release induced by intravenous lipopolysaccharide (LPS) in rats previously treated with intracerebroventricular (i.c.v.) saline, L-NAME, L-arginine or sodium nitroprusside (SNP). In control rats given i.c.v. saline, L-NAME, L-arginine or SNP, AVP levels did not change from baseline. After LPS, plasma AVP increased, reaching a peak at 60 min, and returning to basal levels 4 h later in all i.c.v. pre-treated groups (P<0.05). The LPS administration in rats previously treated with L-NAME induced higher AVP levels (P<0.05) that remained elevated throughout the period of the experiment (P<0.05). These findings confirm the inhibitory role of NO in AVP secretion induced by LPS.