RESUMEN
Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.
Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Oxitocina , Receptores de Oxitocina , Femenino , Humanos , Masculino , Metilación de ADN , Epigénesis Genética , Oxitocina/sangre , Receptores de Oxitocina/genética , Receptores de Oxitocina/metabolismo , Trastornos Relacionados con Cocaína/sangre , Trastornos Relacionados con Cocaína/genéticaRESUMEN
The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.
Asunto(s)
Epilepsia Refleja , Hipotálamo/metabolismo , Excitación Neurológica/fisiología , Sistemas Neurosecretores/metabolismo , Neurohipófisis/metabolismo , Estimulación Acústica , Animales , Modelos Animales de Enfermedad , Epilepsia Refleja/genética , Epilepsia Refleja/metabolismo , Epilepsia Refleja/patología , Epilepsia Refleja/fisiopatología , Regulación de la Expresión Génica , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Hipotálamo/patología , Hipotálamo/fisiopatología , Excitación Neurológica/patología , Masculino , Sistemas Neurosecretores/patología , Sistemas Neurosecretores/fisiopatología , Oxitocina/sangre , Oxitocina/genética , Oxitocina/metabolismo , Neurohipófisis/patología , Neurohipófisis/fisiopatología , Ratas , Ratas Wistar , Convulsiones/genética , Convulsiones/metabolismo , Convulsiones/fisiopatología , Convulsiones/psicología , Vasopresinas/sangre , Vasopresinas/genética , Vasopresinas/metabolismoRESUMEN
Sepsis promotes an inflammatory state in the central nervous system (CNS) that may cause autonomic, cognitive, and endocrine changes. Microglia, a resident immune cell of the CNS, is activated in several brain regions during sepsis, suggesting its participation in the central alterations observed in this disease. In this study, we aimed to investigate the role of microglial activation in the neuroendocrine system functions during systemic inflammation. Wistar rats received an intracerebroventricular injection of the microglial activation inhibitor minocycline (100 µg/animal), shortly before sepsis induction by cecal ligation and puncture. At 6 and 24 h after surgery, hormonal parameters, central and peripheral inflammation, and markers of apoptosis and synaptic function in the hypothalamus were analyzed. The administration of minocycline decreased the production of inflammatory mediators and the expression of cell death markers, especially in the late phase of sepsis (24 h). With respect to the endocrine parameters, microglial inhibition caused a decrease in oxytocin and an increase in corticosterone and vasopressin plasma levels in the early phase of sepsis (6 h), while in the late phase, we observed decreased oxytocin and increased ACTH and corticosterone levels compared to septic animals that did not receive minocycline. Prolactin levels were not affected by minocycline administration. The results indicate that microglial activation differentially modulates the secretion of several hormones and that this process is associated with inflammatory mediators produced both centrally and peripherally.
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Corticosterona/sangre , Microglía/metabolismo , Oxitocina/sangre , Sepsis/metabolismo , Vasopresinas/sangre , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Masculino , Microglía/efectos de los fármacos , Minociclina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Sistemas Neurosecretores/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Morbidity and mortality from cardiovascular disease is a typical phenomenon in the elderly, and are related to unfavorable genetic, hormonal and environmental (lifestyle) interactions. In this context, oxytocin (OT) seems plays a key role in the development of CVD by performing important actions in metabolism energy and hemodynamic variables. OBJECTIVE: To verify if there is an association between (OT) levels and the oxytocin receptor gene (OXTR) polymorphism (rs2254298) with cardiovascular risk factors (CRF) in the elderly. METHODS: This was a cross-sectional study in community-dwelling elderly attending primary health care. The genotyping was done using the polymerase chain reaction technique. The CRF factors investigated included hypertension, diabetes mellitus, dyslipidemia, sedentary lifestyle, and obesity. Levels of triglycerides (TGC) postprandial and glucose were measured in capillary blood. OT and cortisol levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The sample comprised 177 elderly individuals. OT levels showed a significant negative correlation with postprandial triglycerides (pâ¯=â¯0.030) and BMI (pâ¯=â¯0.019). OT levels were also associated with leanness (pâ¯=â¯0.005). On Poisson regression analysis, OT remained a predictor for leanness (pâ¯=â¯0.010). No significant associations were observed between the OXTR polymorphism and CRF. CONCLUSION: The results suggest that Postprandial TGC levels are increased, while OT levels are decreased, and this hormone was significantly elevated in lean elderly. Future studies are needed to confirm these findings, and the role of OT in metabolic parameters.
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Enfermedades Cardiovasculares/etiología , Oxitocina/sangre , Polimorfismo Genético , Receptores de Oxitocina/genética , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Atención Primaria de Salud , Factores de Riesgo , Triglicéridos/sangreRESUMEN
A considerable increase in creatinine kinase (CK) activity and gastrin hormone due to exercise has been observed in sled dogs during endurance mushing races; however, there have been no studies on sled dogs during recreational mushing. Although oxytocin hormone is involved in social behaviors and empathy, it has not been studied in sled dogs. This study aimed to assess changes in plasma CK activity, and gastrin and oxytocin concentrations in adult sled dogs used in touristic mushing in North Patagonia, Argentina. Blood samples were collected before, during, and after the winter season of 2017. Creatinine kinase activity measurement was done using an enzymatic assay. Hormone analyses were performed using commercial Enzyme-Linked InmunoSorbent Assay kits. Results showed an expected two-fold increase in CK activity during the winter, with recovering basal values after winter (< 400 UI/L), low and stable levels of gastrin (9.4 ± 8.8 pg/mL), and a slight increase in oxytocin (23%) after mushing activities. No evidence indicated gastrin alterations or muscular damage from touristic mushing, but an oxytocin increase would indicate a stimulation of the brain reward system.
Asunto(s)
Perros/sangre , Perros/fisiología , Esfuerzo Físico/fisiología , Animales , Argentina , Creatina Quinasa/sangre , Femenino , Gastrinas/sangre , Masculino , Oxitocina/sangreRESUMEN
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.
Asunto(s)
Conducta Animal/efectos de los fármacos , Corticosterona/sangre , Riñón/efectos de los fármacos , Oxitocina/sangre , Efectos Tardíos de la Exposición Prenatal/metabolismo , Cloruro de Sodio/farmacología , Animales , Ingestión de Líquidos/efectos de los fármacos , Femenino , Riñón/metabolismo , Lactancia/fisiología , Masculino , Embarazo , Ratas , Ratas Wistar , Micción/efectos de los fármacos , Micción/fisiología , Privación de Agua/fisiología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
INTRODUCTION: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. OBJECTIVE: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). MATERIALS AND METHODS: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. RESULTS: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. CONCLUSIONS: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.
Asunto(s)
Hormona Adrenocorticotrópica/sangre , Arginina Vasopresina/sangre , Corticosterona/sangre , Hormona Liberadora de Corticotropina/sangre , Privación Materna , Oxitocina/sangre , Hormona Adrenocorticotrópica/metabolismo , Animales , Arginina Vasopresina/metabolismo , Corticosterona/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Sistema Hipotálamo-Hipofisario/crecimiento & desarrollo , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Oxitocina/metabolismo , Sistema Hipófiso-Suprarrenal/crecimiento & desarrollo , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Ratas WistarRESUMEN
Besides their well-established endocrine roles, vasopressin and oxytocin are also important regulators of immune function, participating in a complex neuroendocrine-immune network. In the present study, we investigated whether and how vasopressin and oxytocin could modulate lipopolysaccharide (LPS)-induced nitric oxide (NO) production in a well-established model of experimental endotoxaemia. Male Wistar rats were previously treated i.v. with vasopressin V1 or oxytocin receptor antagonists and then received either an i.v. LPS injection to induce endotoxaemia or a saline imjection as a control. The animals were divided into two groups: in the first group, blood was collected at 2, 4 and 6 h after LPS injection; in the second group, mean arterial blood pressure (MABP) and heart rate (HR) were recorded over 6 h. Plasma vasopressin and oxytocin values were higher in LPS- compared to saline-injected animals at 2 and 4 h but returned to basal levels at 6 h. NO levels exhibited an opposite pattern, showing a progressive increase over the entire period. The previous administration of a vasopressin V1 receptor antagonist significantly reduced NO plasma concentrations at 2 and 4 h but not at 6 h. By contrast, oxytocin receptor agonist pre-treatment had no effect on the NO plasma concentration. In relation to MABP, previous treatment with vasopressin V1 receptor antagonist reversed the LPS-induced hypotension at 4 h, although this was not the case for oxytocin antagonist-treated animals. None of the antagonists affected HR. Our findings indicate that vasopressin (but not oxytocin) has effects on NO production during endotoxaemia in rats, although they do not lend support to the proposed anti-inflammatory actions of vasopressin during endotoxaemia.
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Endotoxemia/sangre , Hipotensión/sangre , Óxido Nítrico/sangre , Oxitocina/sangre , Neurohipófisis/metabolismo , Vasopresinas/sangre , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipotensión/inducido químicamente , Lipopolisacáridos/antagonistas & inhibidores , Masculino , Ratas , Receptores de Oxitocina/antagonistas & inhibidores , Factores de TiempoRESUMEN
Introducción. En diversos modelos animales, incluido el de la separación materna durante la lactancia, se ha demostrado que las experiencias tempranas adversas, como el maltrato, el abandono materno y el estrés psicosocial, pueden favorecer el desarrollo de algunas enfermedades mentales, pero no se han descrito completamente varios de los cambios que se producen en el sistema neuroendocrino. Objetivo. Determinar si la separación materna durante la lactancia modificaba los niveles basales de neurohormonas como la corticosterona, la corticotropina (ACTH), la oxitocina y la vasopresina (ADH), en ratas jóvenes (35 días) y adultas (90 días). Materiales y métodos. Se separaron ratas Wistar de sus madres durante dos periodos de tres horas diarias a lo largo de los 21 días de lactancia. A los 35 y 90 días se tomaron muestras de los grupos de las ratas de control y de las separadas de la madre, para obtener el suero y posteriormente medir cada una de las hormonas mediante un ensayo inmunoenzimático. Resultados. Las concentraciones de corticosterona fueron mayores en las hembras adultas de control que en el resto de los grupos, y menores en los machos adultos de control. Las de ACTH fueron mayores en los machos y hembras jóvenes separadas de la madre que en los grupos de adultos. Los niveles de oxitocina fueron significativamente mayores en las hembras adultas separadas de la madre que en los otros grupos y significativamente menores en los machos adultos. En cuanto a la vasopresina, los grupos separados de la madre tuvieron concentraciones menores, en comparación con los grupos de jóvenes y adultos de control. Conclusiones. Estos resultados muestran que el estrés temprano al que fueron sometidas las ratas, produjo cambios en las respuestas del eje hipotálamo-hipófisis-suprarrenal, las cuales variaron según el sexo y la edad.
Introduction: Work with different animal models including that of maternal separation during nursing has shown that early adverse experiences such as abuse, maternal abandonment and psychosocial stress may favor the development of various psychopathologies. However, several neuroendocrine changes have not been completely described yet. Objective: To establish whether maternal separation during nursing modifies the basal levels of neurohormones such as corticosterone, ACTH, oxytocin and vasopressin in juvenile and adult rats (aged 35 and 90 days, respectively). Materials and methods: Wistar rats were separated from their mothers for two periods of 3 hours per day during the 21 days of nursing. Once these rats had reached 35 and then 90 days of age, blood samples were taken from both the separated and control groups to obtain serum for immunoenzymatic assays and measure the levels of each of the hormones. Results: Concentrations of corticosterone were higher in control adult females in comparison with the rest of the groups and lower in the control adult males. Those of ACTH were higher in the separated young males and females than in the adult groups. Oxytocin levels were significantly higher in the separated adult females in comparison with the other groups and significantly lower in the adult males. With respect to vasopressin, the separated groups had lower concentrations than the young and adult control groups. Conclusions: These results show that the early stress to which rats were submitted produced changes in the basal responses of the hypothalamic-pituitary-adrenal axis, that these responses were distinct in males and females and that they also differed according to age.
Asunto(s)
Animales , Femenino , Masculino , Ratas , Arginina Vasopresina/sangre , Corticosterona/sangre , Hormona Liberadora de Corticotropina/sangre , Oxitocina/sangre , Hormona Adrenocorticotrópica/sangre , Privación Materna , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/crecimiento & desarrollo , Arginina Vasopresina/metabolismo , Corticosterona/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Oxitocina/metabolismo , Ratas Wistar , Hormona Adrenocorticotrópica/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/crecimiento & desarrolloRESUMEN
The central control of the micturition is dependent on cortical areas and other ascending and descending pathways in the brain stem. The descendent pathways from the pons to the urinary bladder (UB) can be direct or indirect through medullary neurons (MN). Chemical stimulation with l-glutamate of MN known for their involvement in cardiovascular regulation evokes changes in pelvic nerves activities, which innervate the urinary bladder. Different neurotransmitters have been found in medullary areas; nevertheless, their involvement in UB control is few understood. We focused to investigate if cholinergic activation of neurons in the medulla oblongata changes the urinary bladder activity. Carbachol (cholinergic agonist) or atropine (cholinergic antagonist) was injected into the 4thV in anesthetized female Wistar rats and the intravesical pressure (IP), mean arterial pressure (MAP), heart rate (HR) and renal conductance (RC) were recorded for 30 min. Carbachol injection into the 4thV increased IP with peak response at 30 min after carbachol and yielded no changes in MAP, HR and RC. Atropine injection into the 4thV decreased IP and elicited no changes in MAP, HR and RC. Plasma vasopressin levels evaluated by ELISA kit assay increased after carbachol into the 4th V. Intravenous blockade of V1 receptors prior to carbachol into the 4thV abolished the increase in IP evoked by carbachol. Therefore, our findings suggest that cholinergic activation of neurons in the medulla oblongata by carbachol injections into the 4thV increases IP due to plasma vasopressin release, which acts in V1 receptors in the UB.
Asunto(s)
Acetilcolina/metabolismo , Bulbo Raquídeo/citología , Neuronas/citología , Neuronas/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/fisiología , Vasopresinas/sangre , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas/farmacología , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Presión Arterial/efectos de los fármacos , Atropina/farmacología , Carbacol/farmacología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Bulbo Raquídeo/fisiología , Oxitocina/sangre , Ratas , Ratas Wistar , Receptores de Vasopresinas/metabolismo , Vasopresinas/metabolismoRESUMEN
During dehydration, responses of endocrine and autonomic control systems are triggered by central and peripheral osmoreceptors and peripheral baroreceptors to stimulate thirst and sodium appetite. Specifically, it is already clear that endocrine system acts by secreting vasopressin (AVP), oxytocin (OT) and angiotensin II (ANG II), and that gaseous molecules, such as nitric oxide (NO) and carbon monoxide (CO), play an important role in modulating the neurohypophyseal secretion as well as ANG II production and thirst. More recently, another gas-hydrogen sulfide (H2S)-has been studied as a neuronal modulator, which is involved in hypothalamic control of blood pressure, heart frequency and temperature. In this study, we aimed to investigate whether H2S and its interaction with NO system could participate in the modulatory responses of thirst and hormonal secretion induced by fluid deprivation. For this purpose, Wistar male rats were deprived of water for 12 and 24h, and the activity of sulfide-generating enzymes was measured. Surprisingly, 24-h water deprivation increased the activity of sulfide-generating enzymes in the medial basal hypothalamus (MBH). Furthermore, the icv injection of sodium sulfide (Na2S, 260nmol), a H2S donor, reduced water intake, increased AVP, OT and CORT plasma concentrations and decreased MBH nitrate/nitrite (NOX) content of 24-h water-deprived animals compared to controls. We thus suggest that H2S system has an important role in the modulation of hormonal and behavioral responses induced by 24-h fluid deprivation.
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Ingestión de Líquidos/efectos de los fármacos , Gasotransmisores/farmacología , Sulfuro de Hidrógeno/farmacología , Neurotransmisores/farmacología , Oxitocina/sangre , Vasopresinas/sangre , Privación de Agua/fisiología , Animales , Masculino , Oxitocina/efectos de los fármacos , Ratas , Ratas Wistar , Vasopresinas/efectos de los fármacosRESUMEN
Septic shock is a serious condition with a consequent drop in blood pressure and inadequate tissue perfusion. Small-volume resuscitation with hypertonic saline (HS) has been proposed to restore physiological haemodynamics during haemorrhagic and endotoxic shock. In the present study, we sought to determine the effects produced by an HS infusion in rats subjected to caecal ligation and perforation (CLP). Male Wistar rats were randomly grouped and submitted to either CLP or sham surgery. Either HS (7.5% NaCl, 4 ml kg(-1) i.v.) or isotonic saline (IS; 0.9% NaCl, 4 ml kg(-1) i.v.) was administered 6 h after CLP. Recordings of mean arterial pressure and heart rate were made during this protocol. Moreover, measurements of electrolyte, vasopressin and oxytocin secretion were analysed after either the HS or the IS treatment. Six hours after CLP, we observed a characteristic decrease in mean arterial pressure that occurs after CLP. The HS infusion in these rats produced a transient elevation of the plasma sodium concentration and osmolality and increased plasma vasopressin and oxytocin levels. Moreover, the HS infusion could restore the mean arterial pressure after CLP, which was completely blunted by the previous injection of the vasopressin but not the oxytocin antagonist. The present study demonstrated that rats subjected to CLP and an infusion of hypertonic saline respond with secretion of neurohypophyseal hormones and a transient increase in blood pressure mediated by the V(1) receptor.
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Presión Arterial , Fluidoterapia/métodos , Neurohipófisis/fisiopatología , Solución Salina Hipertónica/administración & dosificación , Choque Séptico/terapia , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas , Presión Arterial/efectos de los fármacos , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Homeostasis , Antagonistas de Hormonas/farmacología , Infusiones Intravenosas , Masculino , Concentración Osmolar , Oxitocina/sangre , Neurohipófisis/efectos de los fármacos , Neurohipófisis/metabolismo , Ratas , Ratas Wistar , Receptores de Oxitocina/antagonistas & inhibidores , Receptores de Oxitocina/metabolismo , Receptores de Vasopresinas/metabolismo , Choque Séptico/sangre , Choque Séptico/fisiopatología , Sodio/sangre , Factores de Tiempo , Vasopresinas/sangre , Equilibrio HidroelectrolíticoRESUMEN
The deactivation of the inhibitory mechanisms with injections of moxonidine (α2-adrenoceptor/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) increases hypertonic NaCl intake by intra- or extracellular dehydrated rats. In the present study, we investigated the changes in the urinary sodium and volume, sodium balance, and plasma vasopressin and oxytocin in rats treated with intragastric (i.g.) 2 M NaCl load (2 ml/rat) combined with injections of moxonidine into the LPBN. Male Holtzman rats (n=5-12/group) with stainless steel cannulas implanted bilaterally into LPBN were used. Bilateral injections of moxonidine (0.5 nmol/0.2 µl) into the LPBN decreased i.g. 2 M NaCl-induced diuresis (4.6±0.7 vs. vehicle: 7.4±0.6 ml/120 min) and natriuresis (1.65±0.29 vs. vehicle: 2.53±0.17 mEq/120 min), whereas the previous injection of the α2-adrenoceptor antagonist RX 821002 (10 nmol/0.2 µl) into the LPBN abolished the effects of moxonidine. Moxonidine injected into the LPBN reduced i.g. 2 M NaCl-induced increase in plasma oxytocin and vasopressin (14.6±2.8 and 2.2±0.3 vs. vehicle: 25.7±7 and 4.3±0.7 pg/ml, respectively). Moxonidine injected into the LPBN combined with i.g. 2 M NaCl also increased 0.3 M NaCl intake (7.5±1.7 vs. vehicle: 0.5±0.2 mEq/2 h) and produced positive sodium balance (2.3±1.4 vs. vehicle: -1.2±0.4 mEq/2 h) in rats that had access to water and NaCl. The present results show that LPBN α2-adrenoceptor activation reduces renal and hormonal responses to intracellular dehydration and increases sodium and water intake, which facilitates sodium retention and body fluid volume expansion.
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Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Plexo Braquial , Deshidratación/metabolismo , Hormonas/sangre , Imidazoles/farmacología , Receptores de Imidazolina/agonistas , Riñón/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Antagonistas Adrenérgicos alfa/farmacología , Animales , Arginina Vasopresina/sangre , Factor Natriurético Atrial/sangre , Volumen Sanguíneo/efectos de los fármacos , Deshidratación/patología , Diuresis/efectos de los fármacos , Idazoxan/análogos & derivados , Idazoxan/farmacología , Imidazoles/administración & dosificación , Receptores de Imidazolina/administración & dosificación , Riñón/citología , Masculino , Natriuresis/efectos de los fármacos , Concentración Osmolar , Oxitocina/sangre , Potasio/orina , Ratas , Ratas Sprague-Dawley , Renina/sangre , Sodio/sangre , Sodio/metabolismo , Cloruro de Sodio/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
The present study provides the first in vivo evidence that the cannabinoid CB(1) receptor mediates the effects of dexamethasone on hormone release induced by changes in circulating volume and osmolality. Male adult rats were administered with the CB(1) 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. 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 CB(1) receptor. 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 CB(1) receptor regulates AVP secretion independently of glucocorticoid-mediated signalling. 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 CB(1) receptor in the control of peripheral factors that modulate cardiovascular function. Rimonabant also reversed the inhibitory effects of dexamethasone on H-EVE-induced corticosterone secretion, reinforcing the hypothesis that the CB(1) receptor may be involved in the negative feedback exerted by glucocorticoids on the activity of the hypothalamic-pituitary-adrenal axis. Collectively, the results of the present study indicate that the CB(1) 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.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Líquido Extracelular/fisiología , Glucocorticoides/fisiología , Oxitocina/metabolismo , Receptor Cannabinoide CB1/fisiología , Vasopresinas/metabolismo , Animales , Factor Natriurético Atrial/sangre , Volumen Sanguíneo , Líquido Extracelular/efectos de los fármacos , Masculino , Concentración Osmolar , Ósmosis , Oxitocina/sangre , Piperidinas/farmacología , Pirazoles/farmacología , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/antagonistas & inhibidores , Rimonabant , Vasopresinas/sangreRESUMEN
Increased plasma osmolality by food intake evokes augmentation of plasma oxytocin (OT). Ovarian steroids may also influence the balance of body fluids by acting on OT neurones. Our aim was to determine if estrogen influences the activity of OT neurones in paraventricular nucleus (PVN) and supraoptic nucleus (SON) under different osmotic situations. Ovariectomized rats (OVX) were treated with either estradiol (E(2)) or vehicle and were divided into three groups: group I was fed ad libitum, group II underwent 48âh of fasting, and group III was refed after 48âh of fasting. On the day of the experiment, blood samples were collected to determine the plasma osmolality and OT. The animals were subsequently perfused, and OT/FOS immunofluorescence analysis was conducted on neurones in the PVN and the SON. When compared to animals which were fasted or fed ad libitum, the plasma osmolality of refed animals was higher, regardless of whether they were treated with vehicle or E(2). We observed neural activation of OT cells in vehicle- or E(2)-treated OVX rats refed after 48âh of fasting, but not in animals fed ad libitum or in animals that only underwent 48âh of fasting. Finally, the percentage of neurones that co-expressed OT and FOS was lower in both the PVN and the SON of animals treated with E(2) and refed, when compared to vehicle-treated animals. These results suggest that E(2) may have an inhibitory effect on OT neurones and may modulate the secretion of OT in response to the increase of osmolality induced by refeeding.
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Ingestión de Alimentos , Estradiol/metabolismo , Hipotálamo Anterior/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Oxitocina/metabolismo , Equilibrio Hidroelectrolítico , Animales , Femenino , Hipotálamo Anterior/citología , Proteínas del Tejido Nervioso/sangre , Neuronas/citología , Concentración Osmolar , Ovariectomía , Oxitocina/sangre , Núcleo Hipotalámico Paraventricular/citología , Núcleo Hipotalámico Paraventricular/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratas , Ratas Wistar , Núcleo Supraóptico/citología , Núcleo Supraóptico/metabolismo , Transmisión SinápticaRESUMEN
BACKGROUND: The aim of this study was to determine serum oxytocin concentrations following different regimens of prophylactic oxytocin administration in women undergoing elective caesarean delivery. METHODS: Thirty healthy pregnant patients were randomized, after clamping of the umbilical cord, to receive intravenous oxytocin in one of the following groups: G1 (n=9), 10 IU of oxytocin infused over 30 min (0.33 IU/min); G2 (n=11), 10 IU of oxytocin infused over 3 min and 45 s (2.67 IU/min); and G3 (n=10), 80 IU of oxytocin infused over 30 min (2.67 IU/min). Both patient and surgeon were blinded to allocation. Uterine tone was assessed by surgical palpation. Serum oxytocin concentration was determined by enzyme immunoassay before anaesthesia (T0) and at 5 (T5), 30 (T30) and 60 (T60) min after the start of oxytocin infusion. RESULTS: Serum oxytocin concentrations (mean±standard error, ng/mL) were not significantly different in the groups at T0 (0.06±0.02, 0.04±0.02 and 0.07±0.04, respectively, P=0.76), and T60 (0.65±0.26, 0.36±0.26 and 0.69±0.26, respectively, P=0.58). G3 showed higher concentrations than G1 at T5 (3.65±0.74 versus 0.71±0.27, P=0.01) and at T30 (6.19±1.19 versus 1.17±0.37, P<0.01), and were higher than G2 at T30 (6.19±1.19 versus 0.41±0.2, P<0.01). Haemodynamic data and uterine tone were considered satisfactory and similar in all groups. No additional uterotonic agents were needed. CONCLUSION: Serum oxytocin measurements made using enzyme immunoassay in healthy pregnant women undergoing elective caesarean delivery showed that administration of 80 IU oxytocin over 30 min resulted in higher serum oxytocin levels after 5 and 30 min than the two other regimens. The concentrations did not differ between groups at 60 min.
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Cesárea , Oxitócicos/administración & dosificación , Oxitócicos/sangre , Oxitocina/administración & dosificación , Oxitocina/sangre , Adulto , Presión Sanguínea/fisiología , Cromatografía de Afinidad , Parto Obstétrico , Método Doble Ciego , Femenino , Frecuencia Cardíaca/fisiología , Hematócrito , Humanos , Técnicas para Inmunoenzimas , Infusiones Intravenosas , Metaraminol/administración & dosificación , Metaraminol/uso terapéutico , Monitoreo Intraoperatorio , Embarazo , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéuticoRESUMEN
BACKGROUND: Nitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of Nω-nitro-L-arginine methyl ester (L-NAME, 40 µg), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO. RESULTS: Injections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II. DISCUSSION AND CONCLUSION: Thus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.
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Angiotensina II/fisiología , Presión Sanguínea/efectos de los fármacos , Encéfalo/fisiología , Ingestión de Líquidos/fisiología , Óxido Nítrico/fisiología , Angiotensina II/administración & dosificación , Angiotensina II/agonistas , Angiotensina II/antagonistas & inhibidores , Animales , Arginina/administración & dosificación , Arginina/farmacología , Factor Natriurético Atrial/sangre , Encéfalo/efectos de los fármacos , Ingestión de Líquidos/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/farmacología , Oxitocina/sangre , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sodio/metabolismo , Orina/fisiología , Vasopresinas/sangreRESUMEN
This study investigated the participation of the hypothalamic endocannabinoid system in the response to lipopolysaccharide (LPS) challenge evaluating oxytocin (OXT) and tumor necrosis factor-alpha (TNF-alpha) plasma levels in vivo and their release from hypothalamic fragments in vitro. LPS increased OXT and TNF-alpha release through anandamide-activation of hypothalamic cannabinoid receptor CB(1,) since the antagonist AM251 blocked this effect. Anandamide, through its receptors, also increased hypothalamic nitric oxide (NO) which inhibited OXT release, ending the stimulatory effect of the endocannabinoid. Our findings reveal a hypothalamic interaction between oxytocin, endocannabinoid and NO-ergic systems providing a regulation of the hypothalamic-neurohypophyseal axis under basal and stress conditions.
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Moduladores de Receptores de Cannabinoides/metabolismo , Endocannabinoides , Hipotálamo/efectos de los fármacos , Lipopolisacáridos/farmacología , Oxitocina/sangre , Factor de Necrosis Tumoral alfa/sangre , Análisis de Varianza , Animales , Ácidos Araquidónicos/farmacología , Benzamidas/farmacología , Moduladores de Receptores de Cannabinoides/antagonistas & inhibidores , Moduladores de Receptores de Cannabinoides/farmacología , Carbamatos/farmacología , Ensayo de Inmunoadsorción Enzimática/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Hipotálamo/metabolismo , Indoles/farmacología , Masculino , Óxido Nítrico/metabolismo , Alcamidas Poliinsaturadas/farmacología , Radioinmunoensayo/métodos , Ratas , Ratas Sprague-Dawley , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismoRESUMEN
OBJECTIVE: Ascorbic acid represents one of the most important antioxidants and neuromodulators, and plays an important role in the cerebral system. In the present study, we investigated the central effect of ascorbic acid on fluid regulation and electrolyte homeostasis. METHODS: Male Wistar rats were implanted with stainless steel cannulas into the lateral ventricle, and sodiun excretion and urinary volume were measured after intracerebroventricular (i.c.v.) injection of ascorbic acid (200 or 600 nmol/rat). In another set of experiments, vasopressin and oxytocin plasma levels were evaluated 10, 20 and 30 minutes after ascorbic acid i.c.v. injection. RESULTS: The administration of ascorbic acid to conscious rats resulted in a significant decrease in urinary volume and an increase in the renal excretion of sodium, with a concomitant increase in the plasma levels of vasopressin and oxytocin. CONCLUSIONS: These results suggest that ascorbic acid may play a significant role in the central regulation of fluid and electrolyte homeostasis.
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Ácido Ascórbico/administración & dosificación , Natriuresis/efectos de los fármacos , Hormonas Neurohipofisarias/metabolismo , Micción/efectos de los fármacos , Animales , Fármacos Antidiuréticos/administración & dosificación , Sistema Nervioso Central/efectos de los fármacos , Estado de Conciencia , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inyecciones Intraventriculares , Masculino , Oxitocina/sangre , Hormonas Neurohipofisarias/sangre , Ratas , Ratas Wistar , Regulación hacia Arriba/efectos de los fármacos , Vasopresinas/sangre , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on brain monoamines and the serum level of hormones involved in milk synthesis and on the milk ejection reflex in rats were evaluated. Dams were treated with 2.5, 5, 15, 25, 50 or 70mg 2,4-D/kg bw according to two experimental designs: (a) through food from post partum day 1 (PPD 1) to PPD 16 and the respective control groups or (b) an unique i.p. injection on PPD 11. To measure milk ejection, the litter was separated from the mother at the 11th day of lactation during 8h, returned to their mothers and allowed to suckle for a period of 15min. The procedure was repeated on 3 consecutive days until the end of treatment. The change in litter weight during the suckling period was taken as a measure of the amount of milk ejected during this period. The dams' serum prolactin (PRL), oxytocin (OT) and growth hormone levels were determined by radioimmunoassay. Both treatment regimens produced a dose-dependent decrease in the amount of milk ejected and circulating PRL and OT secreted in response to the suckling stimulus. Administration of OT before returning the pups restored the milk ejection, indicating no impairment in the capacity of the mammary gland to produce and secrete milk. In addition, dopamine levels were increased by the 2,4-D treatments in arcuate nucleus (ArN) and anterior lobe of pituitary gland (AL), while serotonin level was drastically decreased in ArN. 2,4-D treatment increased both calcium-dependent and calcium-independent nitric oxide synthase (NOS) activities in ArN. These results suggest that 2,4-D inhibits the suckling-induced hormone release, milk transfer to the litter at the central level, through a stimulation of hypothalamic NOS and dopamine and by an inhibition of hypothalamic serotonin transmission.