Search

Major Depressive Disorder (MDD) directly impacts the lives of countless individuals worldwide, yet its causes remain incompletely understood. However, it is recognized that a deficiency in monoamines, including dopamine, may contribute to this disorder. N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) (CF 3 SePB) is an organoselenium compound that presented antidepressant-like effect in mice related to modulation of serotonergic, but not noradrenergic system. To expand the knowledge about CF 3 SePB mechanisms of action, this study aimed to evaluate the involvement of dopaminergic system in its antidepressant-like effect. Male Swiss mice were pre-treated with the haloperidol (0.05 mg/kg, i.p., a non-selective D 2 receptor antagonist), SCH 23390 (0.01 mg/kg, s.c., a D 1 receptor antagonist), and sulpiride (50 mg/kg, i.p., a D 2 receptor antagonist) 15 min before CF 3 SePB (50 mg/kg, i.g.), and after 30 min of CF 3 SePB administration the forced swimming test (FST) was performed. CF 3 SePB presented an anti-immobility effect in the FST, demonstrated by increase in the latency to first episode of immobility and reduction of total immobility of mice, and the pre-treatment of mice with haloperidol, SCH 23390 and sulpiride prevented these effects, showing that the antidepressant-like effect of CF 3 SePB is related to the modulation of the dopaminergic system, specifically the D 1 and D 2 receptors. In addition, in silico pharmacokinetic profiling of CF 3 SePB predicted its low likelihood of inducing adverse effects and potential to cross the blood-brain barrier. These results expand the understanding of CF 3 SePB mechanisms for its antidepressant-like effect, reinforcing the potential of this organonoselenium compound for developing new antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

1-(2-(4-(4-ethylphenyl)-1H-1,2,3-triazol-1-yl)phenyl)ethanone (ETAP) is a novel hybrid compound containing 1,2,3-triazole and acetophenone. It exhibits antidepressant-like effects in male mice, linked to modulation of serotonergic receptors and monoamine oxidase A (MAO-A) inhibition. This study aimed to evaluate the involvement of the dopaminergic and noradrenergic systems, as well as MAO-B activity inhibition, in the antidepressant-like effect of ETAP in male mice, and to evaluate the antidepressant-like effect of ETAP in female mice. Male mice were treated with different dopaminergic and noradrenergic receptors antagonists 15 min before administering ETAP (1 mg/kg, intragastrically, i.g.). The tail suspension test (TST) was performed 30 minutes later. Different male mice were treated with ETAP (1 mg/kg, i.g.), and 30 minutes later, were euthanized to assess MAO-B activity in the prefrontal cortex and hippocampus. To evaluate the antidepressant-like of ETAP in female mice, ETAP (1 mg/kg, i.g.) was administered, followed by the TST and the forced swimming test (FST) 30 minutes later. The dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally, i.p.), SCH23390 (0.01 mg/kg, subcutaneously, s.c.), and sulpiride (50 mg/kg, i.p.), as well the noradrenergic antagonists prazosin (1 mg/kg, i.p.), yohimbine (1 mg/kg, i.p.), and propranolol (2 mg/kg, i.p.), prevented the antidepressant-like effect of ETAP in the TST. MAO-B activity was unaffected by ETAP in both the prefrontal cortex and hippocampus. ETAP (1 mg/kg, i.g.) induced a significant antidepressant-like effect in female mice in the TST and FST. These findings provide valuable insights into the antidepressant-like effect of ETAP, highlighting its potential for developing more effective depression treatments., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

The damage caused by oxidative and glycative stress to cells accumulates on a daily basis and accelerates aging. Glutathione (GSH), a major antioxidant molecule in living organisms, plays a crucial role in detoxifying the stress-causing substances inherent in cells, such as H 2 O 2 and methylglyoxal (MG), an important intermediate of advanced glycation end-products (AGEs). In this study, we focused on the enhanced antioxidant capacity of the selenium analog of GSH, i.e., selenoglutathione (GSeH), compared to GSH, and examined its effects on the detoxification of stress-causing substances and improvement in cell viability. In cell-free systems, GSeH (1 mM) generated in situ from GSeSeG in the presence of NADPH and glutathione reductase (GR) rapidly reduced more than 80% of 0.1 mM H 2 O 2 , indicating the significant glutathione peroxidase (GPx)-like antioxidant activity of GSeSeG. Similarly, around 50% of 0.5 mM MG was degraded by 0.5 mM GSeH within 30 min through a non-enzymatic mechanism. It was also found that GSeSeG (0.05-0.5 mM) showed glutathione S -transferase (GST)-like activity against 1-chloro-2,4-dinitrobenzene (CDNB), a model substance of oxidative stress-causing toxic materials in cells. Meanwhile, HeLa cells that had been pre-treated with GSeSeG exhibited increased viability against 1.2 mM H 2 O 2 (at [GSeSeG] = 0.5-50 μM) and 4 mM MG (at [GSeSeG] = 3 μM), and the latter effect was maintained for two days. Thus, GSeSeG is a potential antioxidant and antiglycative stress agent for cells.

Rationale: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects., Objective: To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF 3 SePB) in mice and the involvement of the serotonergic and noradrenergic systems., Methods: Male Swiss mice were treated with CF 3 SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF 3 SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT 1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT 2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT 3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT 4 receptor antagonist), prazosin (1 mg/kg, i.p., an α 1 -adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α 2 -adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF 3 SePB (50 mg/kg, i.g.), and after 30 min of CF 3 SePB administration the FST was performed., Results: CF 3 SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT 1A and 5-HT 3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF 3 SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice., Conclusion: This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

1-(Phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) is a selenoindolizine with an antidepressant-like effect in mice by regulation of the serotonergic system. This study investigated the involvement of dopaminergic and noradrenergic systems in the antidepressant-like action of MeSeI. For this purpose, Swiss male mice were pretreated with different antagonists, after 15 min, the MeSeI was administrated by intragastric (i.g.) via; after 30 min, the mouse behavior was assessed in the forced swimming test (FST). The action of MeSeI on the activity of monoamine oxidase (MAO) was determined. The pretreatment of mice with haloperidol (0.05 mg/kg, intraperitoneally, i.p.; non-selective dopamine receptor antagonist), sulpiride (50 mg/kg, i.p.; D 2 receptor antagonist), yohimbine (1 mg/kg, i.p.; α 2 receptor antagonist), and propranolol (2 mg/kg, i.p.; non-selective β receptor antagonist), inhibited the anti-immobility action of MeSeI (50 mg/kg, i.g.) in the FST. This blocking effect was not observed when SCH23390 (0.01 mg/kg, i.p.; D 1 receptor antagonist), and prazosin (1 mg/kg, i.p.; α 1 receptor antagonist) were administered. The coadministration of subeffective doses of bupropion (3 mg/kg. i.g.; dopamine and noradrenaline reuptake inhibitor) and MeSeI (0.5 mg/kg. i.g.) reduced the immobility time in the FST. Furthermore, MeSeI inhibited MAO-A and B activities in vitro and ex vivo tests. These results suggest that MeSeI exerts its antidepressant-like effect via regulation of the D 2 , α 2 , and β 1 receptors and the inhibition of MAO-A and B activities. Molecular docking investigations corroborated these results. This study provides comprehensive insights into the antidepressant-like mechanism of MeSeI in mice, suggesting its potential as a novel antidepressant candidate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules produced naturally by the body and by external factors. When these species are generated in excessive amounts, they can lead to oxidative stress, which in turn can cause cellular and tissue damage. This damage is known to contribute to the aging process and is associated with age-related conditions, including cardiovascular and neurodegenerative diseases. In recent years, there has been an increased interest in the development of compounds with antioxidant potential to assist in the treatment of disorders related to oxidative stress. In this way, compounds containing sulfur (S) and/or selenium (Se) have been considered promising due to the relevant role of these elements in the biosynthesis of antioxidant enzymes and essential proteins with physiological functions. In this context, studies involving heterocyclic nuclei have significantly increased, notably highlighting the indolizine nucleus, given that compounds containing this nucleus have been demonstrating considerable pharmacological properties. Thus, the objective of this research was to evaluate the in vitro antioxidant activity of eight S- and Se-derivatives containing indolizine nucleus and different substituents. The in vitro assays 1,1-diphenyl-2-picryl-hydrazil (DPPH) scavenger activity, ferric ion (Fe 3+ ) reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and protein carbonylation (PC) were used to access the antioxidant profile of the compounds. Our findings demonstrated that all the compounds showed FRAP activity and reduced the levels of TBARS and PC in mouse brains homogenates. Some compounds were also capable of acting as DPPH scavengers. In conclusion, the present study demonstrated that eight novel organochalcogen compounds exhibit antioxidant activity., Competing Interests: Eder João Lenardão is an Academic Editor for PeerJ., (©2024 Schossler Garcia et al.)

Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

Rationale: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results., Objectives and Methods: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg)., Results: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT 2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT 4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT 1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT 3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT 2A , 5 -HT 2C , and 5-HT 4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice., Conclusion: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The genus Urochloa includes most of the important grasses and hybrids currently used as pastures in the tropical regions. Cytogenetic analyzes have identified some aneuploid hybrids that provide new perspectives for genetic breeding. The objective was to analyze the meiotic behavior in euploid (2n = 4x = 36) and aneuploid (2n = 4x = 36 + 2) hybrids of U. ruziziensis x U. decumbens and U. ruziziensis x U. brizantha. Later, the chromosomes and respective genomes involved in pairing configurations and abnormalities were identified through GISH, with an emphasis on tracking the behavior of the additional chromosomes in the aneuploid hybrid U. ruziziensis x U. decumbens (B 1 B 2 B 2 B 2 genomes). The aneuploid U. ruziziensis x U. decumbens shows a higher frequency of univalents, reduction of bivalents, and higher index of irregularities compared with the euploid hybrid. For the aneuploid U. ruziziensis x U. brizantha, there was a reduction in the frequency of univalents, an increase in bivalent and trivalent rates and a lower frequency of abnormalities when compared with the euploid hybrid. The rates of meiotic abnormalities and pairing configurations are parental genotype-dependent and influenced by trisomy. The chromosomes of the B 1 and B 2 genomes of the aneuploid hybrid (U. ruziziensis x U. decumbens) are involved in the formation of univalents, bivalents, and multivalents in inter-, intra- and inter-intragenomic pairings. In general, the segregation times of chromosomes of the genomes are different, since the chromosomes of the B 1 genome segregate more slowly.

The development of new drugs to treat painful and inflammatory clinical conditions continues to be of great interest. The present study evaluated the antinociceptive and anti-inflammatory effects of 4-phenylselenyl-7-chloroquinoline (4-PSQ). Mice were orally (p.o.) pretreated with 4-PSQ (0.1-25mg/kg), meloxicam (25mg/kg, a reference drug) or vehicle, 30min prior to the acetic acid, formalin, hot-plate and open-field tests. 4-PSQ reduced abdominal writhing induced by acetic acid and it caused an increase in latency time in the hot-plate test. 4-PSQ inhibited early and late phases of nociception and reduced the paw edema caused by formalin. Locomotor and exploratory activities in the open field test were not altered by treatments. In addition, a time-response curve was carried out by administration of 4-PSQ (25mg/kg; p.o.) at different times before the acetic acid injection. The antinociceptive effect in inhibiting acetic acid-induced abdominal writhing of 4-PSQ started at 0.5h and remained significant up to 4h after administration. Indeed, the anti-inflammatory and antioxidant properties of 4-PSQ were investigated. 4-PSQ diminished the edema formation and decreased the myeloperoxidase activity and reactive species levels induced by croton oil in the ear tissue. 4-PSQ partially protected against the decrease of the 2,2'-Azinobis-3-ethylbenzothiazoline 6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) levels induced by croton oil. Meloxicam presented similar results for 4-PSQ in tests evaluated. These results demonstrated that 4-PSQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Previous studies revealed the presence of LTC(4) synthase in paraventricular vasopressinergic neurons, suggesting a role for leukotrienes (LTs) in certain neuroendocrine system functions. Our aim was to study the effect of an inhibitor of LT synthesis in the release of arginine vasopressin (AVP) following an osmotic stimulus in rats. Male Wistar rats received an intra-cerebroventricular injection of 2 μl of the LT synthesis inhibitor MK-886 (1, 2, or 4 μg/kg), or vehicle (DMSO 5%), 1h before an intraperitoneal injection of hypertonic saline (NaCl 2M) or isotonic saline (NaCl 0.01 M) in a volume corresponding to 1% of body weight. Thirty minutes after the osmotic stimulus, the animals were decapitated and blood was collected for determining hematocrit, plasma osmolality and plasma AVP levels. As expected, the injection of hypertonic saline significantly increased (P<0.05) the hematocrit, plasma osmolality and plasma AVP levels. While inhibiting LT synthesis by central administration of MK-886 did not cause any additional increase in hematocrit or osmolality, plasma AVP levels were augmented (P<0.05). We conclude that central leukotrienes may have a modulatory role in AVP secretion following an osmotic stimulus, this deserving future studies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The value of the preparation of the colon prior colorectal surgery remains debatable. Since installed as traditional the use of this routine, few studies have been conducted to support the safety of surgeries done without mechanical bowel preparation., Aim: To determine if there is a correlation between postoperative complications and no use of mechanical bowel preparation in operated patients., Methods: Was conducted a prospective study in patients undergoing coloproctology abdominal surgery without prior bowel preparation., Results: The sample consisted of 126 patients, 57 men and 69 women. The average age was 54 years (19 to 89). Among patients who had comorbidities (43 patients - 34,12%), 30 (23,80%) had arterial hypertension. Antibiotic prophylaxis was used in 89,70%. Among the patients, 14,28% had complications: eight (6,34%) wound infection, six (4,76%) anastomotic dehiscence and four (3,17%) fistula., Conclusion: The pre-operative mechanical bowel preparation is not essential in the routine of colorectal surgeries.

Objective: To determine if the magnitude of the force used to induce incisor tooth movement promotes distinct activation in cells in the central amygdala (CEA) and lateral hypothalamus (LH) of rats. Also, the effect of morphine on Fos immunoreactivity (Fos-IR) was investigated in these nuclei., Materials and Methods: Adult male rats were anesthetized and divided into six groups: only anesthetized (control), without orthodontic appliance (OA), OA but without force, OA activated with 30g or 70g, OA with 70g in animals pretreated with morphine (2 mg/kg, intraperitoneal). Three hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing CEA and LH were processed for Fos protein immunohistochemistry., Results: The results show that in the control group, the intramuscular injection of a ketamine/ xylazine mixture did not induce Fos-IR cells in the CEA or in the LH. Again, the without force group showed a little Fos-IR. However, in the 70g group the Fos-IR was the biggest observed (P < .05, Tukey) in the CEA and LH compared with the other groups. In the 30g group, the Fos-IR did not differ from the control group, the without OA group, and the without force group. Furthermore, pretreatment with morphine in the 70g group reduced Fos-IR in these regions., Conclusions: Tooth movement promotes Fos-IR in the CEA and LH according to the magnitude of the force applied.

This study examined whether electrolytic ablation of the periventricular anteroventral third ventricle (AV3V) region would affect the hypothalamic activation and the increase of hypophysial hormone secretion induced by systemic injection of lipopolysaccharide (LPS) in rats. LPS significantly increased the number of cells showing Fos immunoreactivity in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus (P<0.05) and also increased plasma levels of vasopressin, oxytocin, adrenocorticotropin and corticosterone (P<0.05). AV3V lesion significantly reduced LPS-induced Fos immunoreactivity (P<0.05) and vasopressin and oxytocin secretion (P<0.05). Elevations in adrenocorticotropin but not in plasma corticosterone after LPS were affected by prior AV3V lesions. These findings demonstrate that LPS-induced Fos expression in the PVN and SON, and hypophysial hormone secretion is dependent on the integrity of the AV3V region.

During the early phase of endotoxic shock the hypothalamus is activated and neurohypophyseal hormone secretion is increased. In order to study the participation of the subfornical organ (SFO) in this response we lesioned the nucleus and determined hormone secretion and c-fos expression in the paraventricular and supraoptic nuclei after administration of lipopolysaccharides (LPS) in rats. LPS significantly increased the number of cells showing Fos immunoreactivity in the paraventricular and supraoptic nuclei of the hypothalamus (p < 0.05) and also caused an increase in plasma levels of vasopressin and oxytocin (p < 0.05). SFO lesion significantly reduced LPS-induced Fos immunoreactivity (p < 0.05) and hormone secretion (p < 0.05). We conclude that the SFO participates in the activation of the hypothalamic-neurohypophyseal axis in the early phase of endotoxic shock.

Lipopolysaccharides (LPS) can be used to induce experimental endotoxic shock, which is characterized by a significant decrease in mean arterial pressure (MAP) and a decreased vasoconstrictor response that have been attributed to excessive nitric oxide production. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), in addition to lowering serum cholesterol levels, exert many pleiotropic effects, including anti-inflammatory action. In the present study, we investigated the effect of simvastatin, an HMG-CoA reductase inhibitor, on the production of nitric oxide and the cardiovascular response to LPS. Male Wistar rats were pretreated with different doses of simvastatin (10, 20, 40, and 80 mg/kg, i.p.) or saline 20 min before i.v. injection of LPS (1.5 mg/kg) or saline (control). MAP was continuously recorded and nitrate plasma concentration was determined during the 6-h experimental session at 1-h intervals. The pressor response to phenylephrine (1 microg/kg) was evaluated before and 6 h after LPS administration. In the LPS-treated group, there was a time-dependent increase in nitrate plasma concentration (P<0.001), and this response was decreased in simvastatin pretreated rats (P<0.001). We also observed that LPS decreased the pressor response to phenylephrine (P<0.001), an effect that was reverted by simvastatin pretreatment (P<0.05). However, simvastatin did not modify the decrease of MAP induced by LPS. We concluded that simvastatin decreases nitrate plasma concentration in response to LPS and recovers vascular responsiveness during an experimental endotoxic shock. These data suggest the potential use of HMG-CoA reductase inhibitors as a coadjuvant in the treatment of septic shock.

Experiments were performed to study angiotensin (Ang) AT1a and AT1b mRNA expression in mice, including, examination of brain distribution and the effect of salt loading. In situ hybridization (ISH) methods showed that the pattern of mRNA expression was identical for AT1a and AT1b, with cellular labeling in rostral forebrain, hypothalamus and brainstem. Receptor mRNAs were concentrated in brain regions involved in the regulation of electrolyte and cardiovascular balance. Immunocytochemistry with AT1 specific antisera showed a pattern that was consistent with the ISH. Reverse transcriptase-polymerase chain reaction (RT-PCR) of hypothalamus and pituitary verified the presence of both AT1a and AT1b mRNA. Using quantitative ISH, we found that AT1a mRNA expression was significantly increased after 5 days of 2% NaCl consumption in anterior third ventricle (AV3V), paraventricular hypothalamus (PVN) and subfornical organ (SFO), but unchanged in anterior pituitary. There were no significant changes in AT1b mRNA. These results document the utility of ISH coupled with quantitative imaging techniques for the study of subtype specific expression. Using ISH and RT-PCR, we verified that AT1a and AT1b receptors are expressed in mouse brain and pituitary and show a similar pattern of distribution. Salt loading produced a specific increase in AT1a mRNA in osmosensitive regions, suggesting that this receptor subtype is regulated by sodium/osmolar input.

Sinoaortic baroreceptor denervation is reported to produce exaggerated centrally derived cardiovascular and endocrine responses. We examined the effect of sinoaortic denervation (SAD) on the cardiovascular and endocrine responses to two acute stressors, footshock and immobilization, in male Sprague-Dawley rats. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and plasma levels of oxytocin (OT) and vasopressin (VP). Baseline MAP was elevated in the SAD group (approximately 25 mm Hg) and footshock stress increased arterial pressure equivalently in both groups. This stress caused tachycardia and increased plasma OT, with a tendency for the SAD group to show blunted responses. Immobilization increased HR but caused no change in MAP and no significant difference between the groups. This form of stress also increased plasma OT, and again the SAD group showed a diminished response. Plasma VP was not significantly altered by either stressor. The results of these studies indicate that SAD does not uniformly increase the cardiovascular and endocrine responses to all stressors or centrally derived stimuli. These results also suggest that the lack of an increase in plasma VP is not related to baroreceptor-mediated inhibition of secretion under stressful conditions.

The microinjection of hypertonic sodium chloride into the third ventricle elicits natriuresis and kaliuresis in rats following water loading. These responses were blocked by atropine or phentolamine microinjection into the MSA. The data suggest the interaction between periventricular areas sensible to changes of sodium concentration in the cerebrospinal fluid (CSF) and MSA. Cholinergic and alpha-adrenergic synapses of MSA are involved in this interaction which regulates renal sodium excretion.