What is the central question of this study? The central goal of this study was to understand the effects of central angiotensin-(1-7) on basal and osmotically stimulated water intake in rats. What is the main finding and its importance? This study demonstrated that central administration of angiotensin-(1-7) did not induce thirst in basal conditions but increased water intake after osmotic stimulation, such as water deprivation and salt loading. These results indicate a new function for this peptide, which, in turn, allows for future research on the mechanisms through which angiotensin-(1-7) influences osmotic thirst. Angiotensin-(1-7) [Ang-(1-7)] is generated by type 2 angiotensin-converting enzyme (ACE2) and binds to the MAS receptor. Although it is well known that Ang-(1-7) functionally antagonizes the effects of the classical renin-angiotensin system in several situations, the role of Ang-(1-7) in hydromineral homeostasis is not clear. The aim of this study was to assess the role of Ang-(1-7) on neuroendocrine responses to hyperosmolality in rats. Male Wistar rats were divided into the following three groups: control; 24 h of water deprivation (WD); and 24 h of salt loading (SL; 1.8% NaCl). Intracerebroventricular (i.c.v.) injections of Ang-(1-7) or vehicle were given to assess water intake and plasma concentration of vasopressin. Additionally, the brains from control and WD groups were collected to evaluate gene expression in the subfornical organ (SFO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). It was found that i.c.v. Ang-(1-7) did not change water and salt intake in control rats; however, Ang-(1-7) increased water intake after WD and SL, with no change in salt intake. Plasma vasopressin was not changed by i.c.v. Ang-(1-7) in control or WD rats. Moreover, WD increased Mas gene expression in the SON and PVN, with no changes in Ace2 mRNA levels. In conclusion, Ang-(1-7) increases thirst after osmotic stimuli, indicating that a previous sensitization to its action is necessary. This finding is consistent with the increased Mas gene expression in the PVN and SON after water deprivation.
New Findings What is the central question of this study?Can Na+ depletion mobilize Na+ from the skin reservoir in ovariectomized rats? Does oestrogen replacement change the amount and the dynamics of skin Na+ storage? Is the reduced salt appetite after Na+ depletion in ovariectomized rats with oestrogen replacement related to changes in the skin Na+? What is the main finding and its importance?This work demonstrated that acute body Na+ depletion induced by frusemide mobilized the osmotically inactive skin Na+ reservoir to become osmotically active. Oestrogen treatment decreased the induced Na+ intake in ovariectomized rats but did not modulate the inactive Na+ reservoir in control conditions or its mobilization induced by Na+ depletion. Abstract Oestradiol, which is an important hormone for water and electrolyte balance, also has a role in the inhibition of induced Na+ appetite. Sodium can be stored in the skin in osmotically active or inactive forms, and this skin Na+ reservoir may be involved in the control of body Na+ levels during physiopathological challenges. In this study, we investigated whether the effect of sodium depletion by frusemide can mobilize Na+ from the skin reservoir and whether oestradiol replacement changes or mobilizes the Na+ reserves in the skin. Ovariectomized Wistar rats were treated with vehicle or oestradiol for 7 days to evaluate the effects of oestrogen on the hydroelectrolyte balance, intake responses and skin Na+ and water content in basal conditions. Furthermore, the effects of oestrogen were evaluated after 24 h frusemide‐induced whole‐body Na+ depletion. Oestradiol‐replaced rats exhibited reduced water intake without any significant changes in salt intake, Na+ excretion or water and Na+ skin content in basal conditions. After sodium depletion, both vehicle‐ and oestradiol‐treated rats exhibited an increase in the osmotically active skin Na+, which was associated with a decrease of the inactive skin Na+ reservoir. Oestrogen decreased the hypertonic saline intake induced by Na+ depletion, but it was not associated with any significant changes in the skin Na+ reservoir. Thus, sodium depletion is able to change the inactive–active skin Na+ reservoir balance. However, the oestrogenic modulation of sodium appetite after Na+ depletion is probably not related to the action of this hormone in the skin Na+ reservoir balance.
Besides being recognised for involvement in cardiovascular control and hydromineral balance, the renin‐angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 hours of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal‐associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO‐AT1R signalling in the control of re‐feeding‐induced thirst. On the other hand, i.c.v. losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.This article is protected by copyright. All rights reserved.
Aim: The present study aimed to examine whether apipuncture (stimulation of acupuncture points with bee venom) at ST36 and GV3 acupoints promotes neuroprotection and reduces neuroinflammation by modulating M1 and M2 phenotype polarization. Methods: Wistar rats were treated with bee venom (BV) (0.08 mg/kg) injection at acupoints ST36 and GV3 [BV (ST36 + GV3)-spinal cord injury (SCI)] or BV injection at non-acupoints [BV (NP)-SCI] or no treatment (CTL-SCI) after SCI by compression. The spinal cord mRNA expression of iNOS, Arg-1 and TGF-β was measured by real time PCR and the levels of IBA-1; BCL-2; NeuN e CNPase was measured by western blotting. Locomotor performance was measured by Basso, Beattie, and Bresnahan (BBB) and grid-walking tests. Results: Apipuncture treatment was able to (1) ameliorate locomotor performance; (2) reduce inflammatory markers (Cox-2 levels) and activation of microglia and macrophages; (3) reduce the polarization of the M1 phenotype marker (iNOS) and increase M2 (Arg-1 and TGF-β) phenotypic markers; (4) promote neuroprotection by reducing the death of neurons and oligodendrocytes; and (5) increase the expression of the anti-apoptotic factor BCL-2. Conclusion: Apipuncture treatment induces locomotor recovery and neuroprotection after the compression model of spinal cord injury. Further, it reduces neuroinflammation by decreasing M1 polarization and increasing M2 phenotype.
We intend to examine the effect of repeated use of an agonist of 5‐HT1A receptor in sodium appetitive response in ovariectomized (OVX) rats and investigate the effect of estrogen therapy. Female Wistar rats (n=6‐14) were ovariectomized and formed groups as follow: OVX and OVX + E2 (estradiol cypionate, 80µg/Kg, SC, 14 days) separated in groups of 8‐OH‐DPAT (5‐HT1A receptor agonist, 250µg/Kg, IP, 7 days) or vehicle (0.9% NaCl) in baseline and sodium depletion (furosemide 20mg/kg, SC) protocols. The animals were submitted to following analyses: (i) plasma Na+ (ii) radioimmunoassay to measure oxytocin (OT), vasopressin (AVP), angiotensin II (ANG II) plasma levels. The E2 increased Na+ (P<0.01) plasma levels in OVX‐E2‐8‐OH‐DPAT compared to the OVX‐E2‐OH‐DPAT group in sodium depletion condition. Plasma OT increased (P<0.001) in OVX‐E2‐8‐OH‐DPAT group compared to OVX‐E2 group in baseline condition. OT plasma levels also significantly increased in OVX‐E2 group compared to OVX rats (P<0.01). AVP plasma concentration increased in OVX‐E2‐DPAT group in relation to OVX‐E2 (P<0.001) group following volume depletion. Plasma concentration of ANG II decreased in OVX group compared to OVX‐E2 (P<0.01) group in basal condition. Plasma concentration of ANG II decreased in OVX group compared to OVX‐E2 (P<0.01) group in basal condition. Thus, these results suggest that repeated administration of 5‐HT1A agonist associated with E2 replacement differentially trigger mechanisms for neuroendocrine in electrolyte homeostasis. Grant Funding Source: FAPERJ, CNPq and CAPES
Sodium appetite is regulated by several signalling molecules, among which angiotensin II (Ang II) serves as a key driver of robust salt intake by binding to Ang II type 1 receptors (AT1R) in several regions in the brain. The activation of these receptors recruits the mitogen-activated protein kinase (MAPK) pathway, which has previously been linked to Ang II-induced increases in sodium appetite. Thus, we addressed the involvement of MAPK signalling in the induction of sodium appetite after 4 days of low-sodium diet consumption. An increase in extracellular signal-regulated kinase (ERK) phosphorylation in the laminae terminalis and mediobasal hypothalamus was observed after low-sodium diet consumption. This response was reduced by i.c.v. microinjection of an AT1R antagonist into the laminae terminalis but not the hypothalamus. This result indicates that low-sodium diet consumption activates the MAPK pathway via Ang II/AT1R signalling on the laminae terminalis. On the other hand, activation of the MAPK pathway in the mediobasal hypothalamus after low-sodium diet consumption appears to involve another extracellular mediator. We also evaluated whether a low-sodium diet could increase the sensitivity for Ang II in the brain and activate the MAPK pathway. However, i.c.v. injection of Ang II increased ERK phosphorylation on the laminae terminalis and mediobasal hypothalamus; this increase achieved a response magnitude similar to those observed in both the normal and low-sodium diet groups. These data indicate that low-sodium diet consumption for 4 days is insufficient to change the ERK phosphorylation response to Ang II in the brain. To investigate whether the MAPK pathway is involved in sodium appetite after low-sodium diet consumption, we performed i.c.v. microinjections of a MAPK pathway inhibitor (PD98059). PD98059 inhibited both saline and water intake after low-sodium diet consumption. Thus, the MAPK pathway is involved in promoting the sodium appetite after low-sodium diet consumption.
Series of studies support an estrogen modulation upon the serotonergic system activity. Thus, we examined the endocrine response in ovariectomized (OVX) rats submitted to oil or estrogen treatment (OVX‐E2, 80microg/kg, SC, 14 days) and to treatment with the 8‐OH‐DPAT(250microg/kg, 7 days) or vehicle (0.9% NaCl) during 7 days), in basal condition and after sodium depletion. We also investigated a possible correlation between serotonergic functional status and E2 replacement on the plasma levels of angiotensin I and II(ANG I, II), oxytocin (OT) and corticosterone (CORT) in basal condition and after sodium depletion. The ANG I and ANG II release and respective mechanisms seem to be depending of the condition of the animal or 8‐OH‐DPAT treatment. Chronic 8‐OH‐DPAT in basal condition increased the ANG I plasma concentration while the E2 seems to attenuate this response following sodium depletion. The OT and CORT plasma levels at basal condition were enhanced by association of the two treatments. E2 replacement, both at baseline and depletion conditions, increased OT and CORT plasma levels. Additionally we did not observe estrogen influence on plasma CORT concentrations following sodium depletion. Both serotonergic signaling as estrogen may be considered controlling systems of electrolyte homeostasis.
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