RESUMO
BACKGROUND: We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS). METHODS: Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer's lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis. RESULTS: At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate. CONCLUSION: In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.
Assuntos
Coração/fisiopatologia , Rim/fisiopatologia , Pulmão/fisiopatologia , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Coração/efeitos dos fármacos , Infusões Intravenosas , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/terapia , Lactato de Ringer/administração & dosagem , Lactato de Ringer/toxicidade , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Aeglids are unique freshwater decapods whose habitats are being impacted by metallic compounds, such as copper (Cu). Thus, we investigated the effects of acute Cu exposure on ionic regulation of Aegla castro. For this, male specimens in intermolt were collected from a reference stream and acclimated for 5 days in laboratory. After which, crabs were exposed to 11 µg L-1 Cu (Cu11) or only to water (CTR) for 24 h. Hemolymph samples were withdrawn for the determination of Na+, K+, Ca2+, and Mg2+ concentrations and the posterior gills removed for the analysis of Na+/K+-ATPase, Ca2+-ATPase, H+-ATPase, and carbonic anhydrase (CA) activities. Increased Ca2+ and Mg2+ hemolymph concentrations were observed in animals from Cu11, when compared with CTR group. In addition, decreased activity of CA was observed in animals exposed to Cu. In the current study, alterations in Ca2+ and Mg2+concentrations probably indicate that animals activated exoskeleton reabsorption mechanisms, characteristic of the premolt. Therefore, increased Ca2+ and Mg2+ concentrations in hemolymph may indicate that a biochemical signal associated with the molting cycle was triggered by Cu exposure. Despite the known harmful effects of Cu on osmoregulatory enzymes, here we observed decreased activity only in CA. However, decreased activity of CA could trigger both acid-base imbalance and ionic disruption, since CA provides H+ and HCO3- for intracellular pH maintenance, and underpins Na+ and Cl- for ionic regulation. Therefore, understanding how aeglids respond to metal contamination in laboratory conditions is crucial to assess their potential as an alternative biological model for aquatic ecotoxicology.
Assuntos
Braquiúros/efeitos dos fármacos , Cobre/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores , Braquiúros/fisiologia , Inibidores da Anidrase Carbônica/toxicidade , Anidrases Carbônicas/metabolismo , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Masculino , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.
Assuntos
Diuréticos/farmacologia , Furosemida/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sódio/metabolismo , Transcriptoma/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Animais , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Transcriptoma/fisiologia , Vasopressinas/metabolismo , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
This study investigated the alkalinizing potential of an intravenous polyionic solution containing 84 mEq/L of lactate on hydroelectrolyte and acid-base balances in healthy goats.Four solutions, containing 28 and 84 mEq/L of lactate (L28 and L84) or bicarbonate (B28 and B84), were formulated. Six healthy Saanen goats were used. All four solutions were infused intravenously in each animal, one at a time, with an interval of 45 days between the infusions, at a speed of 33.3 mL/kg/h and totaling a volume equivalent to 10% of their body weight, in 3 h of continuous administration. Samples of venous blood and urine were collected at 0h (start of the infusion), 1.5h (middle of the infusion), 3h (end of the infusion), and 4.5h, 6h, and 24 h from the start of the infusion. The laboratory tests included determination of blood pH, pCO2, HCO3-, base excess (BE), Na+, K+, Cl-, total plasmatic protein, L-lactate, and creatinine. In urine samples, pH, Na+, K+, Cl-, L-lactate, and creatinine were measured. The L28 solution, equivalent to lactated Ringer's solution, caused a slight increase in the alkaline reserve and did not change the electrolyte balance. The L84 solution resulted in a greater increase in the alkaline reserve, equivalent to the B84 solution, with return to baseline values within 24 h from the start of the infusion.The L84 solution proved to be safe and produced iatrogenic alkalization when infused into healthy goats, without causing side effects.(AU)
O objetivo deste trabalho foi investigar o potencial alcalinizante de uma solução poli-iônica intravenosa contendo 84mEq/L de lactato no equilíbrio hidroeletrolítico e ácido base de cabras saudáveis. Quatro soluções contendo 28 e 84 mEq/L de lactato (L28 e L84) ou bicarbonato (B28 e B84) foram formuladas. Seis cabras, adultas, da raça Saanen, saudáveis receberam as quatro soluções por via intravenosa, uma de cada vez, com intervalo de quatro a cinco dias entre as infusões, a velocidade de 33,3 ml/kg/h, totalizando um volume equivalente a 10% do seu peso corporal, em três horas de administração contínua. Foram coletadas amostras de sangue venoso e urina antes do início da infusão (0h), na metade (1,5h), no fim (3h) e às 4,5h, 6h e 24h após o início da infusão. Os exames laboratoriais consistiram na determinação do pH sanguíneo, pCO2, HCO3-, BE, Na+, K+, Cl-, proteína plasmática total, lactato L e creatinina. Nas amostras de urina foram medidos o pH, Na+, K+, Cl-, lactato L e creatinina. A solução L28, equivalente à solução de Ringer com lactato, causou um aumento leve na reserva alcalina e não alterou o equilíbrio eletrolítico. A solução L84 resultou em maior aumento da reserva alcalina, equivalente à solução B84, com retorno dos parâmetros avaliados aos valores basais em até 24 horas após o início da infusão. A solução L84 provou-se segura e produziu alcalose iatrogência em cabras sadias, sem causar qualquer efeito colateral.(AU)
Assuntos
Animais , Feminino , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Alcalose/veterinária , Cabras/sangue , Cabras/urinaRESUMO
This study investigated the alkalinizing potential of an intravenous polyionic solution containing 84 mEq/L of lactate on hydroelectrolyte and acid-base balances in healthy goats.Four solutions, containing 28 and 84 mEq/L of lactate (L28 and L84) or bicarbonate (B28 and B84), were formulated. Six healthy Saanen goats were used. All four solutions were infused intravenously in each animal, one at a time, with an interval of 45 days between the infusions, at a speed of 33.3 mL/kg/h and totaling a volume equivalent to 10% of their body weight, in 3 h of continuous administration. Samples of venous blood and urine were collected at 0h (start of the infusion), 1.5h (middle of the infusion), 3h (end of the infusion), and 4.5h, 6h, and 24 h from the start of the infusion. The laboratory tests included determination of blood pH, pCO2, HCO3-, base excess (BE), Na+, K+, Cl-, total plasmatic protein, L-lactate, and creatinine. In urine samples, pH, Na+, K+, Cl-, L-lactate, and creatinine were measured. The L28 solution, equivalent to lactated Ringer's solution, caused a slight increase in the alkaline reserve and did not change the electrolyte balance. The L84 solution resulted in a greater increase in the alkaline reserve, equivalent to the B84 solution, with return to baseline values within 24 h from the start of the infusion.The L84 solution proved to be safe and produced iatrogenic alkalization when infused into healthy goats, without causing side effects.
O objetivo deste trabalho foi investigar o potencial alcalinizante de uma solução poli-iônica intravenosa contendo 84mEq/L de lactato no equilíbrio hidroeletrolítico e ácido base de cabras saudáveis. Quatro soluções contendo 28 e 84 mEq/L de lactato (L28 e L84) ou bicarbonato (B28 e B84) foram formuladas. Seis cabras, adultas, da raça Saanen, saudáveis receberam as quatro soluções por via intravenosa, uma de cada vez, com intervalo de quatro a cinco dias entre as infusões, a velocidade de 33,3 ml/kg/h, totalizando um volume equivalente a 10% do seu peso corporal, em três horas de administração contínua. Foram coletadas amostras de sangue venoso e urina antes do início da infusão (0h), na metade (1,5h), no fim (3h) e às 4,5h, 6h e 24h após o início da infusão. Os exames laboratoriais consistiram na determinação do pH sanguíneo, pCO2, HCO3-, BE, Na+, K+, Cl-, proteína plasmática total, lactato L e creatinina. Nas amostras de urina foram medidos o pH, Na+, K+, Cl-, lactato L e creatinina. A solução L28, equivalente à solução de Ringer com lactato, causou um aumento leve na reserva alcalina e não alterou o equilíbrio eletrolítico. A solução L84 resultou em maior aumento da reserva alcalina, equivalente à solução B84, com retorno dos parâmetros avaliados aos valores basais em até 24 horas após o início da infusão. A solução L84 provou-se segura e produziu alcalose iatrogência em cabras sadias, sem causar qualquer efeito colateral.
Assuntos
Feminino , Animais , Alcalose/veterinária , Cabras/sangue , Cabras/urina , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.
Assuntos
Humanos , Aspirina/intoxicação , Aspirina/metabolismo , Fibrinolíticos/intoxicação , Fibrinolíticos/metabolismo , Overdose de Drogas/fisiopatologia , Overdose de Drogas/terapia , Acidose/induzido quimicamente , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Aspirina/administração & dosagem , Overdose de Drogas/metabolismo , Hipoglicemia/induzido quimicamente , Hipotensão/induzido quimicamente , Mitocôndrias/efeitos dos fármacosRESUMO
OBJECTIVES: To determine the relationship between theophylline trough levels and urine output in critically ill children administered aminophylline as adjunctive diuretic therapy. DESIGN: Retrospective cohort study. SETTING: The PICU of a tertiary care children's hospital. PATIENTS: A mixed population of medical/surgical including postoperative cardiothoracic surgery patients less than 18 years old. INTERVENTIONS: Electronic medical records of all PICU patients admitted from July 2010 to June 2015 were reviewed, and patients who received aminophylline as diuretic therapy were identified. MEASUREMENTS AND MAIN RESULTS: Patient cohort data including demographics, daily aminophylline, furosemide and chlorothiazide dosing, theophylline trough levels, fluid intake, urine output and total fluid balance, blood urea nitrogen, and creatinine levels were abstracted. Multivariate analysis based on a generalized estimating equations approach demonstrated that aminophylline administration, when analyzed as a categorical variable, was associated with an increase in urine output and decreased fluid balance. However, aminophylline dosing, when analyzed as a continuous variable, was associated with neither an increase in urine output nor decreased fluid balance. Theophylline trough levels were not correlated with urine output at 24 hours (p = 0.78) and were negatively correlated with urine output at 48 hours (r = 0.078; p < 0.005). CONCLUSIONS: Aminophylline administration provided a measure of increased diuresis, regardless of dosage, and theophylline trough levels. Therefore, achieving a prescribed therapeutic trough level may not be necessary for full diuretic effect. Because, as opposed to the diuretic effect, the side effect profile of aminophylline is dose-dependent, low maintenance dosing may optimize the balance between providing adjunctive diuretic effect while minimizing the risk of toxicity.
Assuntos
Aminofilina/administração & dosagem , Diuréticos/administração & dosagem , Hidratação/métodos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Administração Intravenosa , Aminofilina/sangue , Aminofilina/farmacocinética , Criança , Pré-Escolar , Estado Terminal , Diuréticos/sangue , Diuréticos/farmacocinética , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Análise de Regressão , Estudos RetrospectivosAssuntos
Aspirina/metabolismo , Aspirina/intoxicação , Overdose de Drogas/fisiopatologia , Overdose de Drogas/terapia , Fibrinolíticos/metabolismo , Fibrinolíticos/intoxicação , Acidose/induzido quimicamente , Aspirina/administração & dosagem , Overdose de Drogas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipotensão/induzido quimicamente , Mitocôndrias/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
PURPOSE: The adherence to and effectiveness and safety of a timed, electronic, assessment-driven potassium-replacement protocol (TARP) were compared with an electronic nurse-driven replacement protocol (NRP) are reported. METHODS: A retrospective observational study was conducted in a community hospital evaluating protocol adherence, effectiveness, and safety for 2 potassium-replacement protocols. All adults on medical units with an order for potassium replacement per protocol during the 3-month trial periods were reviewed. All patients requiring potassium replacement per protocol were included in the analysis. Adherence to the protocol was assessed by evaluating the dose of potassium administered and performance of reassessments. Effectiveness of the protocol was assessed by evaluating the time to achieve target potassium levels. Safety was assessed by evaluating the route of administration and occurrence of hyperkalemia. RESULTS: A total of 300 patients treated using potassium-replacement protocols required potassium replacement during the study period, with 148 patients in the NRP group requiring 491 instances of potassium replacement. In the TARP group a total of 564 instances requiring potassium replacement corresponded to 152 patients. Of the 491 instances requiring replacement in the NRP group, the correct dose was administered and reassessment performed 117 times (23.8%). Overall adherence (p < 0.05), correct dose given (p < 0.05), average time from blood draw to potassium replacement (p < 0.0001), use of oral replacement (p < 0.05), and time to achieve target potassium level within 12 hours (p < 0.05) were significantly improved in the TARP group. CONCLUSION: The TARP improved the effectiveness and safety of potassium-replacement therapy over the traditional NRP without negatively affecting timeliness of care.
Assuntos
Protocolos Clínicos , Monitoramento de Medicamentos/métodos , Prescrição Eletrônica , Hidratação/métodos , Potássio/sangue , Monitoramento de Medicamentos/instrumentação , Feminino , Hidratação/instrumentação , Hospitais Comunitários/métodos , Humanos , Masculino , Potássio/administração & dosagem , Estudos Retrospectivos , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
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.
Assuntos
Comportamento Animal/efeitos dos fármacos , Corticosterona/sangue , Rim/efeitos dos fármacos , Ocitocina/sangue , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Cloreto de Sódio/farmacologia , Animais , Ingestão de Líquidos/efeitos dos fármacos , Feminino , Rim/metabolismo , Lactação/fisiologia , Masculino , Gravidez , Ratos , Ratos Wistar , Micção/efeitos dos fármacos , Micção/fisiologia , Privação de Água/fisiologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Fluid and electrolyte status have a significant impact on physical performance and health. Pre-exercise recommendations cite the possibility of consuming beverages with high amounts of sodium. In this sense, non-alcoholic beer can be considered an effective pre-exercise hydration beverage. This double-blind, randomized study aimed to compare the effect of beer, non-alcoholic beer and water consumption before exercise on fluid and electrolyte homeostasis. Seven male soccer players performed 45 min of treadmill running at 65% of the maximal heart rate, 45 min after ingesting 0.7 L of water (W), beer (AB) or non-alcoholic beer (NAB). Body mass, plasma Na⺠and K⺠concentrations and urine specific gravity (USG) were assessed before fluid consumption and after exercise. After exercise, body mass decreased (p < 0.05) in W (-1.1%), AB (-1.0%) and NAB (-1.0%). In the last minutes of exercise, plasma Na⺠was reduced (p < 0.05) in W (-3.9%) and AB (-3.7%), plasma K⺠was increased (p < 0.05) in AB (8.5%), and USG was reduced in W (-0.9%) and NAB (-1.0%). Collectively, these results suggest that non-alcoholic beer before exercise could help maintain electrolyte homeostasis during exercise. Alcoholic beer intake reduced plasma Na⺠and increased plasma K⺠during exercise, which may negatively affect health and physical performance, and finally, the consumption of water before exercise could induce decreases of Na⺠in plasma during exercise.
Assuntos
Cerveja , Líquidos Corporais/fisiologia , Exercício Físico/fisiologia , Homeostase/fisiologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Água , Adolescente , Atletas , Método Duplo-Cego , Humanos , Masculino , Corrida , Adulto JovemRESUMO
Hydroelectrolytic imbalances, such as saline load (SL), trigger behavioral and neuroendocrine responses, such as thirst, hypophagia, vasopressin (AVP) and oxytocin (OT) release and hypothalamuspituitaryadrenal (HPA) axis activation. To investigate the participation of the type-1 cannabinoid receptor (CB1R) in these homeostatic mechanisms,male adult Wistar rats were subjected to SL (0.3MNaCl) for four days. SL induced not only increases in the water intake and plasma levels of AVP, OT and corticosterone, as previously described, but also increases in CB1R expression in the lamina terminalis, which integrates sensory afferents, aswell as in the hypothalamus, the main integrative and effector area controlling hydroelectrolytic homeostasis. A more detailed analysis revealed that CB1R-positive terminals are in close apposition with not only axons but also dendrites and secretory granules of magnocellular neurons, particularly vasopressinergic cells. In satiated and euhydrated animals, the intracerebroventricular administration of the CB1R selective agonist ACEA (0.1 µg/5 µL) promoted hyperphagia, but this treatment did not reverse the hyperosmolality-induced hypophagia in the SL group. Furthermore, ACEA pretreatment potentiated water intake in the SL animals during rehydration as well as enhanced the corticosterone release and prevented the increase in AVP and OT secretion induced by SL. The same parameters were not changed by ACEA in the animals whose daily food intake was matched to that of the SL group (Pair-Fed). These data indicate that CB1Rs modulate the hydroelectrolytic balance independently of the food intake during sustained hyperosmolality and hypovolemia.
Assuntos
Metabolismo Energético/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Cloreto de Sódio na Dieta/farmacologia , Equilíbrio Hidroeletrolítico , Animais , Ingestão de Alimentos/efeitos dos fármacos , Endocanabinoides/farmacologia , Metabolismo Energético/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hipovolemia/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Exposure to an altered osmotic environment during a pre/postnatal period can differentially program the fluid intake and excretion pattern profile in a way that persists until adulthood. However, knowledge about the programming effects on the underlying brain neurochemical circuits of thirst and hydroelectrolyte balance, and its relation with behavioral outputs, is limited. We evaluated whether early voluntary intake of hypertonic NaCl solution may program adult offspring fluid balance, plasma vasopressin, neural activity, and brain vasopressin and angiotensinergic receptor type 1a (AT1a)-receptor gene expression. The manipulation (M) period covered dams from 1 week before conception until offspring turned 1-month-old. The experimental groups were (i) Free access to hypertonic NaCl solution (0.45 M NaCl), food (0.18% NaCl) and water [M-Na]; and (ii) Free access to food and water only [M-Ctrol]. Male offspring (2-month-old) were subjected to iv infusion (0.15 ml/min) of hypertonic (1.5M NaCl), isotonic (0.15M NaCl) or sham infusion during 20 min. Cumulative water intake (140 min) and drinking latency to the first lick were recorded from the start of the infusion. Our results indicate that, after systemic sodium overload, the M-Na group had increased water intake, and diminished neuronal activity (Fos-immunoreactivity) in the subfornical organ (SFO) and nucleus of the solitary tract. They also showed reduced relative vasopressin (AVP)-mRNA and AT1a-mRNA expression at the supraoptic nucleus and SFO, respectively. The data indicate that the availability of a rich source of sodium during the pre/postnatal period induces a long-term effect on drinking, neural activity, and brain gene expression implicated in the control of hydroelectrolyte balance.
Assuntos
Encéfalo/citologia , Ingestão de Líquidos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Neurônios/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Solução Salina Hipertônica/efeitos adversos , Fatores Etários , Animais , Animais Recém-Nascidos , Feminino , Seguimentos , Masculino , Gravidez , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores de Tempo , Vasopressinas/genética , Vasopressinas/metabolismo , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 µg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 µg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 µg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 µg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 µg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic.
Assuntos
Saxitoxina/análogos & derivados , Bloqueadores dos Canais de Sódio/toxicidade , Animais , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Saxitoxina/administração & dosagem , Saxitoxina/sangue , Saxitoxina/toxicidade , Bloqueadores dos Canais de Sódio/administração & dosagem , Bloqueadores dos Canais de Sódio/sangue , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
BACKGROUND: Leptospirotic renal lesions frequently produce a polyuric form of acute kidney injury with a urinary concentration defect. Our study investigated a possible effect of the glycolipoprotein, (GLPc) extracted from L. interrogans, on vasopressin (Vp) action in the guinea pig inner medullary collecting duct (IMCD). METHODS: The osmotic water permeability (Pf µm/s) was measured by the microperfusion in vitro technique. AQP2 protein abundance was determined by Western Blot. Three groups were established for study as follows: Group I, IMCD from normal (ngp, nâ=â5) and from leptospirotic guinea-pigs (lgp-infected with L. interrogans serovar Copenhageni, GLPc, nâ=â5); Group II, IMCD from normal guinea-pigs in the presence of GLPc (GLPc group, nâ=â54); Group III, IMCD from injected animals with GLPc ip (nâ=â8). RESULTS: In Group I, PFS were: ngp--61.8±22.1 and lgp--8.8±12.4, p<0.01 and the urinary osmolalities were: lgp--735±64 mOsm/Kg and ngp--1,632±120 mOsm/Kg. The lgp BUN was higher (176±36 mg%) than the ngp (56±9 mg%). In Group II, the Pf was measured under GLPc (250 µg/ml) applied directly to the bath solution of the microperfused normal guinea-pig IMCDs. GLPc blocked Vp (200 pg/ml, nâ=â5) action, did not block cAMP (10(-4) M), and Forskolin (Fors--10(-9) M) action, but partially blocked Cholera Toxin (ChT--10(-9) M) action. GLP from L.biflexa serovar patoc (GLPp, non pathogenic, 250 µg) did not alter Vp action. In Group III, GLPc (250 µg) injected intraperitoneally produced a decrease of about 20% in IMCD Aquaporin 2 expression. CONCLUSION: The IMCD Pf decrease caused by GLP is evidence, at least in part, towards explaining the urinary concentrating incapacity observed in infected guinea-pigs.
Assuntos
Proteínas de Bactérias/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas/farmacologia , Túbulos Renais Coletores/efeitos dos fármacos , Leptospira interrogans/metabolismo , Leptospirose/patologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Animais , Aquaporina 2/metabolismo , Western Blotting , Regulação da Expressão Gênica/fisiologia , Glicoproteínas/isolamento & purificação , Cobaias , Túbulos Renais Coletores/fisiologia , Leptospirose/microbiologia , Permeabilidade , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
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.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Plexo Braquial , Desidratação/metabolismo , Hormônios/sangue , Imidazóis/farmacologia , Receptores de Imidazolinas/agonistas , Rim/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Arginina Vasopressina/sangue , Fator Natriurético Atrial/sangue , Volume Sanguíneo/efeitos dos fármacos , Desidratação/patologia , Diurese/efeitos dos fármacos , Idazoxano/análogos & derivados , Idazoxano/farmacologia , Imidazóis/administração & dosagem , Receptores de Imidazolinas/administração & dosagem , Rim/citologia , Masculino , Natriurese/efeitos dos fármacos , Concentração Osmolar , Ocitocina/sangue , Potássio/urina , Ratos , Ratos Sprague-Dawley , Renina/sangue , Sódio/sangue , Sódio/metabolismo , Cloreto de Sódio/farmacologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
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.
Assuntos
Solução Salina Hipertônica/farmacologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Feminino , Furosemida/farmacologia , Masculino , Imagem Molecular/métodos , Imagem Molecular/estatística & dados numéricos , Gravidez , Ratos , Ratos Wistar , Sódio/deficiência , Sódio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
Amino acids are known to play relevant roles as osmolytes in various tissues, including the retina. Taurine is one of these active molecules. In addition, taurine stimulates outgrowth from the goldfish retina by mechanisms that include extracellular matrix, calcium fluxes and protein phosphorylation. The present report aims to explore the effect of medium osmolarity on goldfish retinal outgrowth and the possible modifications produced by changing eye osmolarity on amino acid levels in the retina. Goldfish retinal explants were obtained 10 days after crush of the optic nerve and cultured under iso-, hypo- or hyper-osmotic conditions. Hypo-osmotic medium was prepared by diluting the solutions 10% twice, preserving fetal calf serum concentration. Hyper-osmotic medium was done by adding 50 or 100 mM urea or mannitol. Evaluation of length and density of neurites was performed 5 days after plating. Outgrowth was reduced in hypo- and in hyper-osmotic conditions. Taurine, 4 mM, increased length and density of neurites in iso-osmotic, and produced stimulatory effects under both hyper-osmotic conditions. The in vivo modification of osmolarity by intraocular injection of water or 100 mM urea modified levels of free amino acids in the retina. Taurine and aspartate retinal levels increased in a time-dependent manner after hypo- and hyper-osmotic solution injections. Serine, threonine, arginine, γ-aminobutyric acid, alanine and tyrosine were elevated in hyper-osmotic conditions. Outgrowth in vitro, after in vivo osmolarity changes, was higher in the absence of taurine, but did not increase in the presence of the amino acid. The fact that certain outgrowth took place in these conditions support that the impairment was not due to tissue damage. Rather, the effects might be related to the cascade of kinase events described during osmolarity variations. The time course under these conditions produced adjustments in ganglion cells probably related to taurine transporter, and phosphorylation of specific proteins.
Assuntos
Aminoácidos/metabolismo , Diferenciação Celular/fisiologia , Carpa Dourada/crescimento & desenvolvimento , Neuritos/metabolismo , Retina/crescimento & desenvolvimento , Retina/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Aminoácidos/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Soluções Hipertônicas/metabolismo , Soluções Hipertônicas/farmacologia , Soluções Hipotônicas/metabolismo , Soluções Hipotônicas/farmacologia , Neuritos/efeitos dos fármacos , Neuritos/ultraestrutura , Técnicas de Cultura de Órgãos , Concentração Osmolar , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
Formation water (produce water or oil field brine) from oil and gas production usually has high concentrations of soluble salts and metals. The objective of this study was to examine the effect of formation water from Urucu Reserve, Amazon, on whole-body uptake and internal distribution of newly accumulated Na+ in juvenile tamoatá, Hoplosternum litoralle. Groups of fish were submitted to nine treatments for 3 h in 400-ml chambers: control (well water), 5% formation water, and well water with respective concentrations of 5% formation water of Ca2+, Fe, Mn, Ba2+, Fe+Ca2+, Mn+Ca2+, and Ba+Ca2+ added. Specimens of tamoatá exposed to 5% formation water presented a very high Na+ influx, probably due to the high Na+ levels in this water. Waterborne Fe and Mn stimulated Na+ influx, but Fe increased Na+ efflux, causing Na+ loss. Waterborne Mn, on the other hand, decreased Na+ efflux, reducing Na+ loss by this species. Waterborne Ca2+ also affected Na+ influx but had no significant effect on net Na+ fluxes. These results demonstrated that spilling of formation water in ion-poor Amazon rivers would dramatically disrupt osmoregulatory balance of tamoatá and probably other Amazon fish species, impairing their survival and reduce biodiversity.