Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride and sucrose intake in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Opioid activation in the lateral parabrachial nucleus induces hypertonic sodium intake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride intake during cell dehydration

Background: Activation of GABAB receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABAB receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used.Results: In fluid replete rats, baclofen (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 μl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABAB antagonist, 5 nmol/0.2 μl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate.Conclusions: Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure. © 2013 Kimura et al.; licensee BioMed Central Ltd.

Availability of a rich source of sodium during the perinatal period programs the fluid balance restoration pattern in adult offspring

Osmoregulatory mechanisms can be vulnerable to electrolyte and/or endocrine environmental changes during the perinatal period, differentially programming the developing offspring and affecting them even in adulthood. The aim of this study was to evaluate whether availability of hypertonic sodium solution during the perinatal period may induce a differential programming in adult offspring osmoregulatory mechanisms. With this aim, we studied water and sodium intake after Furosemide-sodium depletion in adult offspring exposed to hypertonic sodium solution from 1 week before mating until postnatal day 28 of the offspring, used as a perinatal manipulation model [PM-Na group]. In these animals, we also identified the cell population groups in brain nuclei activated by Furosemide-sodium depletion treatment, analyzing the spatial patterns of Fos and Fos-vasopressin immunoreactivity. In sodium depleted rats, sodium and water intake were significantly lower in the PM-Na group vs. animals without access to hypertonic sodium solution [PM-Ctrol group]. Interestingly, when comparing the volumes consumed of both solutions in each PM group, our data show the expected significant differences between both solutions ingested in the PM-Ctrol group, which makes an isotonic cocktail: however, in the PM-Na group there were no significant differences in the volumes of both solutions consumed after Furosemide-sodium depletion, and therefore the sodium concentration of total fluid ingested by this group was significantly higher than that in the PM-Ctrol group. With regard to brain Fos immunoreactivity, we observed that Furosemide-sodium depletion in the PM-Na group induced a higher number of activated cells in the subfornical organ, ventral subdivision of the paraventricular nucleus and vasopressinergic neurons of the supraoptic nucleus than in the PM-Ctrol animals. Moreover, along the brainstem, we found a decreased number of sodium depletion-activated cells within the nucleus of the solitary tract of the PM-Na group. Our data indicate that early sodium availability induces a long-term effect on fluid drinking and on the cell activity of brain nuclei involved in the control of hydromineral balance. These results also suggest that availability of a rich source of sodium during the perinatal period may provoke a larger anticipatory response in the offspring, activating the vasopressinergic system and reducing thirst after water and sodium depletion, as a result of central osmosensitive mechanism alterations. (C) 2011 Elsevier Inc. All rights reserved.

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic ( 5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD- induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD- induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5- HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and nondepleted animals. The OT plasma levels significantly increased only in the PD- induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.

Enhancement of meal-associated hypertonic NaCl intake by moxonidine into the lateral parabrachial nucleus

α2-Adrenoceptor activation with moxonidine (α2-adrenergic/imidazoline receptor agonist) into the lateral parabrachial nucleus (LPBN) enhances angiotensin II/hypovolaemia-induced sodium intake and drives cell dehydrated rats to ingest hypertonic sodium solution besides water. Angiotensin II and osmotic signals are suggested to stimulate meal-induced water intake. Therefore, in the present study we investigated the effects of bilateral injections of moxonidine into the LPBN on food deprivation-induced food intake and on meal-associated water and 0.3 M NaCl intake. Male Holtzman rats with cannulas implanted bilaterally into the LPBN were submitted to 14 or 24 h of food deprivation with water and 0.3 M NaCl available (n = 6-14). Bilateral injections of moxonidine (0.5 nmol/0.2 μl) into the LPBN increased meal-associated 0.3 M NaCl intake (11.4 ± 3.0 ml/120 min versus vehicle: 2.2 ± 0.9 ml/120 min), without changing food intake (11.1 ± 1.2 g/120 min versus vehicle: 11.2 ± 0.9 g/120 min) or water intake (10.2 ± 1.5 ml/120 min versus vehicle: 10.4 ± 1.2 ml/120 min) by 24 h food deprived rats. When no food was available during the test, moxonidine (0.5 nmol) into the LPBN of 24 h food-deprived rats produced no change in 0.3 M NaCl intake (1.0 ± 0.6 ml/120 min versus vehicle: 1.8 ± 1.1 ml/120 min), nor in water intake (0.2 ± 0.1 ml/120 min versus vehicle: 0.6 ± 0.3 ml/120 min). The results suggest that signals generated during a meal, like dehydration, for example, not hunger, induce hypertonic NaCl intake when moxonidine is acting in the LPBN. Thus, activation of LPBN inhibitory mechanisms seems necessary to restrain sodium intake during a meal. © 2007 Elsevier B.V. All rights reserved.

Standardised antibacterial Manuka honey in the management of persistent post-operative corneal oedema: A case series

Background Corneal oedema is a common post-operative problem that delays or prevents visual recovery from ocular surgery. Honey is a supersaturated solution of sugars with an acidic pH, high osmolarity and low water content. These characteristics inhibit the growth of micro-organisms, reduce oedema and promote epithelialisation. This clinical case series describes the use of a regulatory approved Leptospermum species honey ophthalmic product, in the management of post-operative corneal oedema and bullous keratopathy. Methods A retrospective review of 18 consecutive cases (30 eyes) with corneal oedema persisting beyond one month after single or multiple ocular surgical procedures (phacoemulsification cataract surgery and additional procedures) treated with Optimel Antibacterial Manuka Eye Drops twice to three times daily as an adjunctive therapy to conventional topical management with corticosteroid, aqueous suppressants, hypertonic sodium chloride five per cent, eyelid hygiene and artificial tears. Visual acuity and central corneal thickness were measured before and at the conclusion of Optimel treatment. Results A temporary reduction in corneal epithelial oedema lasting up to several hours was observed after the initial Optimel instillation and was associated with a reduction in central corneal thickness, resolution of epithelial microcysts, collapse of epithelial bullae, improved corneal clarity, improved visualisation of the intraocular structures and improved visual acuity. Additionally, with chronic use, reduction in punctate epitheliopathy, reduction in central corneal thickness and improvement in visual acuity were achieved. Temporary stinging after Optimel instillation was experienced. No adverse infectious or inflammatory events occurred during treatment with Optimel. Conclusions Optimel was a safe and effective adjunctive therapeutic strategy in the management of persistent post-operative corneal oedema and warrants further investigation in clinical trials.

Efecto del flujo del dializado sobre la ganancia interdialítica en hemodiálisis crónica (Estudio FLUGAIN)

Objetivos: Determinar si existe diferencia en la ganancia interdialítica entre los pacientes al ser tratados con flujo de dializado (Qd) de 400 mL/min y 500 mL/min. Diseño: Se realizó un estudio de intervención, cruzado, aleatorizado, doble ciego en pacientes con enfermedad renal crónica en hemodiálisis para determinar diferencias en la ganancia de peso interdialítica entre los pacientes tratados con flujo de dializado (Qd) de 400 ml/min y 500 ml/min. Pacientes: Se analizaron datos de 46 pacientes en hemodiálisis crónica con Qd de 400 ml/min y 45 con Qd de 500 ml/min. Análisis: La prueba de hipótesis para evaluar diferencias en la ganancia interdialítica y las otras variables entre los grupos se realizó mediante la prueba T para muestras pareadas. Para el análisis de correlación se calculó el coeficiente de Pearson. Resultados: No hubo diferencia significativa en ganancia interdialítica usando Qd de 400 ml/min vs 500 ml/min (2.37 ± 0.7 vs 2.41 ± 0.6, p=0.41) ni en Kt/V (1.57 ± 0.25 vs 1.59 ± 0.23, p = 0.45), potasio (4.9 ± 1.1 vs 5.1 ± 1.0, p=0.45), fosforo (4.5 ± 1.2 vs 4.4 ± 1.2, p=0.56) o hemoglobina (11.3 ± 1.8 vs 11.3 ± 1.6, p=0.96). Conclusiones: En pacientes con peso ≤ 65 Kg el uso de Qd de 400 ml/min no se asocia con menor ganancia interdialítica de peso. No hay diferencia en la eficiencia de diálisis lo que sugiere que es una intervención segura a corto plazo.

Soluciones hipertónicas en trauma craneoencefálico: revisión sistemática de la literatura

El traumatismo craneoencefálico, es la epidemia silenciosa de nuestra época, que genera gastos en salud, en países como Estados Unidos, cercanos a los 60 billones de dólares anuales, y cerca de 400 billones en rehabilitación de los discapacitados. El pilar del manejo médico del trauma craneoencefálico moderado o severo, es la osmoterapia, principalmente con sustancias como el manitol y las soluciones hipertónicas. Se realizó la revisión de 14 bases de datos, encontrando 4657754 artículos, quedando al final 40 artículos después de un análisis exhaustivo, que se relacionaban con el manejo de la hipertensión endocraneana y terapia osmótica. Resultados: Se compararon diferentes estudios, encontrando gran variabilidad estos, sin homogenización en los análisis estadísticos, y la poca rigurosidad no permitieron, la recolección de datos y la comparación entre los diferentes estudios, no permitió realizar el meta-análisis y por esto se decidió la realización de una revisión sistemática de la literatura. Se evidenció principalmente tres cosas: la primera es la poca rigurosidad con la que se realizan los estudios clínicos; la segunda, es que aún falta mucha más investigación principalmente, la presencia de estudios clínicos aleatorizados multicéntricos, que logren dar una sólida evidencia y que genere validez científica que se requiere, a pesar de la evidencia clara en la práctica clínica; la tercera es la seguridad para su uso, con poca presencia de complicaciones para las soluciones salinas hipertónicas.

Efeitos renais e cardiovasculares da infusão de dopamina e da solução de cloreto de sódio a 7,5%: estudo experimental em cães com restrição hídrica

JUSTIFICATIVA E OBJETIVOS: É controvertido o uso da infusão de dopamina na proteção renal. O objetivo desta pesquisa foi estudar o efeito da dopamina, da solução hipertônica e da associação de ambas em cães com restrição hídrica, simulando o jejum pré-operatório. MÉTODO: Foram estudados, em 32 cães anestesiados com tiopental sódico e fentanil, os seguintes parâmetros da função renal: fluxo plasmático efetivo renal (depuração de para-aminohipurato de sódio), ritmo de filtração glomerular (depuração de creatinina) e as depurações de sódio, de potássio e osmolar, excreção fracionária de sódio e potássio, excreção de sódio e potássio e a resistência vascular renal. Os parâmetros cardiovasculares foram: pressão arterial média, freqüência cardíaca, pressão da veia cava inferior, índice cardíaco, hematócrito e índice de resistência vascular periférica. Os animais foram subdivididos, através de sorteio, em 4 grupos experimentais: Grupo 1 - G1 (n = 8) - grupo controle; Grupo 2 - G2 (n = 8) infusão de dopamina (2 µg.kg-1.min-1), Grupo 3 - G3 (n = 8) solução de cloreto de sódio a 7,5% (2 ml.kg-1) e Grupo 4 - G4 (n = 8) - associação de dopamina (2 µg.kg-1.min-1) e cloreto de sódio a 7,5% (2 ml.kg-1). Os grupos tiveram quatro fases experimentais e cada momento com duração de 30 minutos, compreendendo os momentos M1, M2, M3 e M4. RESULTADOS: O grupo da dopamina (G2) apresentou diminuição da pressão arterial média, da resistência vascular renal e da excreção de potássio. O grupo da solução hipertônica de cloreto de sódio (G3) apresentou aumento do índice cardíaco, do volume urinário, da depuração de sódio e de potássio, da excreção urinária de sódio e potássio e da excreção fracionária de sódio. No grupo da solução hipertônica de cloreto de sódio associada à dopamina (G4), ocorreu elevação da freqüência cardíaca, do índice cardíaco, do fluxo plasmático efetivo renal e da excreção urinária de sódio; ocorreu também diminuição do índice de resistência vascular sistêmica e do potássio plasmático. CONCLUSÕES: Deste estudo conclui-se que a solução hipertônica de cloreto de sódio foi capaz de melhorar as condições hemodinâmicas e, conseqüentemente, a função renal de cães sob restrição hídrica de 12 horas. O mesmo não aconteceu com a infusão de 2 µg.kg-1.min-1 de dopamina que, em situação similar, não causou aumento da diurese e da excreção de sódio.

Respostas cardiovasculares e na ingestão de água e NaCl hipertônico em ratos com doença periodontal tratados com agonista GABAA no núcleo parabraquial lateral

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Participação dos receptores purinérgicos do núcleo do trato solitário no controle da ingestão hidro-mineral

Pós-graduação em Ciências Fisiológicas - FOAR

Antidepressivo modula o comportamento e a expressão gênica das cadeias de miosina, serca2 e fosfolambam em ratos com insuficiência aórtica?

Introduction: Aortic insufficiency (AoI), a volume overload, is characterized by the diastolic reflux of blood from the regurgitating aorta to the left ventricle. This effect results from malfunctioning aortic cusps. The main cause of AoI in developing countries is rheumatic fever, including Brazil, and valvar degeneration in developed countries. There is a strong association between cardiovascular diseases and depression. Selective serotonin reuptake inhibitors (SSRI) are one of the most prescribed antidepressants in the world. Previous studies of our laboratory showed that the utilization of a SSRI, paroxetine, improved cardiac function in rats with sub-chronic AoI and reduced the daily ingestion of hypertonic sodium (NaCl 0,3M). Cardiovascular diseases can determine behavior changes like increase of anxiety, and it is yet unknown if AoI would determine anxiety or anhedonia, incapacity of obtaining pleasure through physical or sensorial experiences. A possible target for SSRI action could be a change in the expression of enzyme isoforms that collaborate in the contractile function of the heart muscle, like the heavy chains of myosine, the sarcoplasmatic reticulum Ca2+/ATPase (SERCA) and its regulator protein, phospholamban (PLB). Objectives: Evaluation of behavior parameters for anxiety and anhedonia state and genic expression of a-myosine, b-myosine, SERCA2a and PLB in the heart tissue of rats with subchronic AoI that received treatment with an SSRI (paroxetine) for 4 weeks. Methods: Surgery to induce AoI was performed on male Wistar rats, anxiety was evaluated by the elevated plus-maze (EPM) and state of anhedonia was tested by ingestion of 2% sucrose solution. After euthanasia the heart tissue was collected and total RNA was extracted to be analyzed by the RT-qPCR method. Results: Heart fractional shortening was preserved in rats with AoI that were treated compared to rats with AoI that were not treated. There was no statistically ...

[The comatose child]

The child who presents with acute coma runs a high risk of cardiopulmonary insufficiency, direct brain injury or even cerebral herniation. The case-management of such child requires a coma-specific emergent evaluation, immediate treatment of any hypoxicischemic insults and of the underlying cause. The coma-specific examination includes performance of child-adapted Glasgow Coma Score, the evaluation of brain stem functions such as pupillary response to light, cough- and gag reflex, and determination of all vital signs including body temperature. Treatment of hypoxicischemic insults includes control of airways and ventilation in patient with coma defined as GCS <8; liberal treatment of impaired cardiovascular states with isotonic fluids such as 0.9% sodium chloride; and treatment of cerebral herniation with head elevation, mannitol, hypertonic sodium chlorid fluids, steroids and hyperventilation. Immediately treatable causes are hypoglycemia, meningitis/encephalitis, opioid overdose and status epilepticus. Exclusion of rapidly progressive intracranial lesions almost always requires referral to the tertiary centre with head CT-scan facilities. Finally, an extensive etiology search of the stable coma is performed by looking for disease or trauma of the brain, for metabolic causes, for intoxications and for cardiopulmonary problems.