Maternal obesity and late effects on offspring metabolism.

OBJECTIVE: The aim of this study was to evaluate the late effects of maternal obesity induced by lesion of the ventromedial hypothalamus on offspring metabolism. MATERIALS AND METHODS: Thirty days after the bilateral lesion of the ventromedial hypothalamus, female rats were mated and divided into 2 groups of pregnant animals: Control (C) - false lesion (sham) and Obese (OB) - lesion. Three months after that, with the groups of mothers, offspring were divided into control and obese animals that received a normocaloric diet (C-N and OB-N), and control and obese animals that received a hypercaloric diet (C-H and OB-H). At 120 days of age, the animals were euthanized and their carcasses, feces and food were submitted to calorimetric analysis to determine energy balance and body composition. RESULTS: During the growth period, offspring from obese mothers showed higher values of body weight and food intake than controls. Obese animals showed higher body weight gain and gross food efficiency than control animals in adulthood. The hypercaloric diet led to increased metabolizable energy intake, percentage of absorbed energy and energy expenditure in both groups. Body composition was only affected by the association of hypercaloric diet and maternal obesity that led to increased body fat. CONCLUSIONS: Maternal obesity has led to the development of later overweight in offspring, suggesting fetal programming. According to the trend presented, it is believed that the prolonged intake of hypercaloric diets in adult animals may, as an additional effect, induce worsening of the overweight induced by maternal obesity.

Maternal obesity and late effects on offspring metabolism / Obesidade materna e efeitos tardios sobre o metabolismo da prole

Objective : The aim of this study was to evaluate the late effects of maternal obesity induced by lesion of the ventromedial hypothalamus on offspring metabolism.Materials and methods : Thirty days after the bilateral lesion of the ventromedial hypothalamus, female rats were mated and divided into 2 groups of pregnant animals: Control (C) – false lesion (sham) and Obese (OB) – lesion. Three months after that, with the groups of mothers, offspring were divided into control and obese animals that received a normocaloric diet (C-N and OB-N), and control and obese animals that received a hypercaloric diet (C-H and OB-H). At 120 days of age, the animals were euthanized and their carcasses, feces and food were submitted to calorimetric analysis to determine energy balance and body composition.Results : During the growth period, offspring from obese mothers showed higher values of body weight and food intake than controls. Obese animals showed higher body weight gain and gross food efficiency than control animals in adulthood. The hypercaloric diet led to increased metabolizable energy intake, percentage of absorbed energy and energy expenditure in both groups. Body composition was only affected by the association of hypercaloric diet and maternal obesity that led to increased body fat.Conclusions : Maternal obesity has led to the development of later overweight in offspring, suggesting fetal programming. According to the trend presented, it is believed that the prolonged intake of hypercaloric diets in adult animals may, as an additional effect, induce worsening of the overweight induced by maternal obesity. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

Objetivo Avaliar os efeitos tardios da obesidade materna induzida por lesão do núcleo ventromedial do hipotálamo sobre o metabolismo da prole. Trinta dias após a lesão bilateral do hipotálamo ventromedial, ratos fêmeas foram colocadas para acasalar e divididas em dois grupos de animais gestantes: Controle (C) – falsa lesão e Obeso (OB) – lesionados. Três meses após o nascimento, de acordo com os grupos das mães, os filhotes foram divididos em animais controle e obesos que recebiam dieta normocalórica (C-N and OB-N) e animais controle e obesos que recebiam dieta hipercalórica (C-H and OB-H). Aos 120 dias de idade, os animais foram eutanasiados e as carcaças, fezes e ração foram submetidas à análise calorimétrica para determinação do balanço energético e composição corporal.Resultados Durante o período de crescimento, os filhos de mães obesas mostraram maiores valores de peso corporal e ingestão alimentar que animais controle. Os animais obesos apresentaram maiores valores de ganho de peso corporal e eficiência metabólica que os animais controle quando adultos. A dieta hipercalórica levou ao aumento da energia metabolizável, percentagem de energia absorvida e gasto energético para ambos os grupos. A composição corporal foi somente afetada pela associação da dieta hipercalórica com a obesidade materna que levou ao aumento da gordura corporal.Conclusões : A obesidade materna levou ao sobrepeso tardio na prole, sugerindo uma programação fetal. Pela tendência apresentada, acreditamos que a ingestão prolongada de dietas hipercalóricas em animais adultos possa induzir uma piora no quadro de sobrepeso induzido pela obesidade materna. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats.

Renal vasodilation and sympathoinhibition are recognized responses induced by hypernatremia, but the central neural pathways underlying such responses are not yet entirely understood. Several findings suggest that A2 noradrenergic neurons, which are found in the nucleus of the solitary tract (NTS), play a role in the pathways that contribute to body fluid homeostasis and cardiovascular regulation. The purpose of this study was to determine the effects of selective lesions of A2 neurons on the renal vasodilation and sympathoinhibition induced by hypertonic saline (HS) infusion. Male Wistar rats (280-350 g) received an injection into the NTS of anti-dopamine-beta-hydroxylase-saporin (A2 lesion; 6.3 ng in 60 nl; n = 6) or free saporin (sham; 1.3 ng in 60 nl; n = 7). Two weeks later, the rats were anesthetized (urethane 1.2 g⋅kg(-1) b.wt., i.v.) and the blood pressure, renal blood flow (RBF), renal vascular conductance (RVC) and renal sympathetic nerve activity (RSNA) were recorded. In sham rats, the HS infusion (3 M NaCl, 1.8 ml⋅kg(-1) b.wt., i.v.) induced transient hypertension (peak at 10 min after HS; 9±2.7 mmHg) and increases in the RBF and RVC (141±7.9% and 140±7.9% of baseline at 60 min after HS, respectively). HS infusion also decreased the RSNA (-45±5.0% at 10 min after HS) throughout the experimental period. In the A2-lesioned rats, the HS infusion induced transient hypertension (6±1.4 mmHg at 10 min after HS), as well as increased RBF and RVC (133±5.2% and 134±6.9% of baseline at 60 min after HS, respectively). However, in these rats, the HS failed to reduce the RSNA (115±3.1% at 10 min after HS). The extent of the catecholaminergic lesions was confirmed by immunocytochemistry. These results suggest that A2 noradrenergic neurons are components of the neural pathways regulating the composition of the extracellular fluid compartment and are selectively involved in hypernatremia-induced sympathoinhibition.

Afferent pathways involved in cardiovascular adjustments induced by hypertonic saline resuscitation in rats submitted to hemorrhagic shock.

The peripheral hyperosmolarity elicited by intravenous infusion of hypertonic saline (HS) can be beneficial in treating hemorrhagic shock. However, the neural mechanisms involved in this resuscitation remain unknown. The present study sought to determine the effects of selective baroreceptor denervation on arterial blood pressure response during HS resuscitation in rats submitted to hemorrhagic shock. Male Wistar rats (280-320 g) were anesthetized with thiopental sodium (40 mg/kg, i.v.), and the femoral artery and jugular vein were cannulated for MAP and heart rate recording and HS infusion (3 mol/L NaCl; 0.18 mL/100 g body weight, >2 min). Hemorrhagic shock was obtained by withdrawing blood over 30 min until a MAP of 60 mmHg was obtained. This level of MAP was maintained for a further 30 min through subsequent blood withdrawal or reinfusion. Next, animals were divided into selective aortic and/or carotid denervation or sham groups before infusing HS. Results showed that in the sham group (n = 12), HS infusion increased MAP to levels close to baseline (from 65 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In the aortic denervated group (n = 10), HS infusion also increased MAP (from 54 +/- 3 to 112 +/- 5 mmHg, 10 min after HS). In contrast, in the carotid denervation group (n = 8), the increase in MAP induced by HS infusion was abolished (from 53 +/- 3 to 73 +/- 12 mmHg, 10 min after HS). These results indicate that in hemorrhaged rats, HS infusion produces a pressor effect that is likely to be mediated through carotid rather than aortic baroreceptors.

Renal sympathoinhibition induced by hypernatremia: involvement of A1 noradrenergic neurons.

Several findings suggest that A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. Recently we demonstrated that the renal vasodilation induced by infusion of hypertonic saline (HS) depends on the integrity of the A1 neurons. Here we determined the effect of lesions of these neurons on the inhibition of the renal sympathetic nerve activity (RSNA) induced by HS infusion. All experiments were performed in Wistar rats (280-350 g). A1 neurons were lesioned by microinjections of antidopamine-beta-hydroxylase-saporin (6.3 ng in 60 nl) into the CVLM (n=5), whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n=10). Two weeks later, rats were anesthetized (urethane 1.2 g/kg, iv), and instrumented for recording of arterial pressure and RSNA. In sham rats, HS infusion (3 M NaCl, 0.18 ml/100 g bw, iv) induced a transient (

Lesions of medullary catecholaminergic neurons increase salt intake in rats.

Several findings suggest that catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. From the CVLM other areas in central nervous system involved in cardiovascular regulation and hydroelectrolyte balance can be activated. Therefore, the aim of the present study was to investigate the effects of lesions of these neurons on 0.3M NaCl and water intake induced by subcutaneous injection of furosemide (FURO)+captopril (CAP) or 36 h of water deprivation/partial hydration with only water (WD/PR). Male Wistar rats (320-360 g) were submitted to medullary catecholaminergic neuron lesions by microinjection of anti-dopamine-beta-hydroxylase-saporin (anti-DbetaH-saporin; 6.3 ng in 60 nl) into the CVLM (SAP-rats). Sham rats received microinjections of free saporin (1.3 ng in 60 nl) in the same region. In SAP-rats, the 0.3M NaCl intake was increased after FURO+CAP (6.8+/-1.0 ml/2h, vs. sham: 3.7+/-0.7 ml/2h) as well as after WD/PR (11.1+/-1.3 ml/2h vs. sham: 6.1+/-1.8 ml/2h). Conversely, in SAP-rats, the water intake induced by FURO+CAP (14.8+/-1.3 ml/2h, vs. sham: 14.1+/-1.6 ml/2h) or by WD/PR (3.6+/-0.9 ml/2h, vs. sham: 3.2+/-1.1 ml/2h) was not different from sham rats. Immunohistochemical analysis indicates that microinjections of anti-DbetaH-saporin produced extensive destruction within the A1 cell groups in the CVLM. These results suggest an inhibitory role for medullary catecholaminergic neurons on sodium appetite.

[Effects of manually assisted coughing on respiratory mechanics in patients requiring full ventilatory support]. / Efeitos da tosse manualmente assistida sobre a mecânica do sistema respiratório de pacientes em suporte ventilatório total.

OBJECTIVE: Manually assisted coughing (MAC) consists of a vigorous thrust applied to the chest at the beginning of a spontaneous expiration or of the expiratory phase of mechanical ventilation. Due to routine use of MAC in intensive care units, the objective of this study was to assess the effects of MAC on respiratory system mechanics in patients requiring full ventilatory support. METHODS: We assessed 16 sedated patients on full ventilatory support (no active participation in ventilation). Respiratory system mechanics and oxyhemoglobin saturation were measured before and after MAC, as well as after endotracheal aspiration. Bilateral MAC was performed ten times on each patient, with three respiratory cycle intervals between each application. RESULTS: Data analysis demonstrated a decrease in resistive pressure and respiratory system resistance, together with an increase in oxyhemoglobin saturation, after MAC combined with endotracheal aspiration. No evidence of alterations in peak pressures, plateau pressures or respiratory system compliance change was observed after MAC. CONCLUSIONS: The use of MAC alters respiratory system mechanics, increasing resistive forces by removing secretions. The technique is considered safe and efficacious for postoperative patients. Using MAC in conjunction with endotracheal aspiration provided benefits, achieving the proposed objective: the displacement and removal of airway secretions.

Efeitos da tosse manualmente assistida sobre a mecânica do sistema respiratório de pacientes em suporte ventilatório total / Effects of manually assisted coughing on respiratory mechanics in patients requiring full ventilatory support

OBJETIVO: A tosse manualmente assistida (TMA) consiste na compressão vigorosa do tórax no início da expiração espontânea ou da fase expiratória da ventilação mecânica. Tendo em vista a utilização rotineira da TMA na unidade de terapia intensiva, a proposta deste estudo foi analisar os efeitos dessa técnica no comportamento da mecânica do sistema respiratório de pacientes submetidos a suporte ventilatório total. MÉTODOS: Foram estudados 16 pacientes intubados, sedados e submetidos à ventilação mecânica controlada, sem participação interativa com o ventilador. A mecânica do sistema respiratório e a saturação periférica de oxigênio foram mensuradas antes e após a aplicação de TMA e após a aspiração traqueal. Foram realizadas 10 aplicações bilaterais da técnica por paciente, com intervalos de 3 ciclos respiratórios entre cada aplicação. RESULTADOS: Os dados evidenciaram a diminuição da pressão resistiva e da resistência do sistema respiratório e aumento da saturação periférica de oxigênio após a aplicação da TMA associada à aspiração traqueal. Não foram evidenciadas alterações das pressões de pico, platô e complacência do sistema respiratório após a aplicação da TMA. CONCLUSÕES: A TMA foi capaz de alterar a mecânica do sistema respiratório, mais especificamente aumentando as forças resistivas através do deslocamento de secreção. A técnica pode ser considerada eficaz e segura para pacientes em pós-operatório imediato. A associação entre TMA e aspiração traqueal mostrou-se benéfica, alcançando os objetivos propostos: deslocamento e remoção de secreção das vias aéreas.

OBJECTIVE: Manually assisted coughing (MAC) consists of a vigorous thrust applied to the chest at the beginning of a spontaneous expiration or of the expiratory phase of mechanical ventilation. Due to routine use of MAC in intensive care units, the objective of this study was to assess the effects of MAC on respiratory system mechanics in patients requiring full ventilatory support. METHODS: We assessed 16 sedated patients on full ventilatory support (no active participation in ventilation). Respiratory system mechanics and oxyhemoglobin saturation were measured before and after MAC, as well as after endotracheal aspiration. Bilateral MAC was performed ten times on each patient, with three respiratory cycle intervals between each application. RESULTS: Data analysis demonstrated a decrease in resistive pressure and respiratory system resistance, together with an increase in oxyhemoglobin saturation, after MAC combined with endotracheal aspiration. No evidence of alterations in peak pressures, plateau pressures or respiratory system compliance change was observed after MAC. CONCLUSIONS: The use of MAC alters respiratory system mechanics, increasing resistive forces by removing secretions. The technique is considered safe and efficacious for postoperative patients. Using MAC in conjunction with endotracheal aspiration provided benefits, achieving the proposed objective: the displacement and removal of airway secretions.

Role of catecholaminergic neurones of the caudal ventrolateral medulla in cardiovascular responses induced by acute changes in circulating volume in rats.

Several findings suggest that catecholaminergic neurones in the caudal ventrolateral medulla (CVLM) contribute to body fluid homeostasis and cardiovascular regulation. The present study sought to determine the effects of lesions of these neurones on the cardiovascular responses induced by changes in circulating volume. All experiments were performed in male Wistar rats (320-360 g). Medullary catecholaminergic neurones were lesioned by microinjection of anti-dopamine beta-hydroxylase-saporin (6.3 ng in 60 nl; SAP rats, n = 14) into the CVLM, whereas sham rats received microinjections of free saporin (1.3 ng in 60 nl, n = 15). Two weeks later, rats were anaesthetized (urethane, 1.2 g kg(-1), i.v.), instrumented for measurement of mean arterial pressure (MAP), renal blood flow (RBF) and renal vascular conductance (RVC), and infused with hypertonic saline (HS; 3 m NaCl, 0.18 ml (100 g body weight)(-1), i.v.) or an isotonic solution (volume expansion, VE; 4% Ficoll, 1% of body weight, i.v.). In sham rats, HS induced sustained increases in RBF and RVC (155 +/- 7 and 145 +/- 6% of baseline, at 20 min after HS). In SAP rats, RBF responses to HS were blunted (125 +/- 6%) and RVC increases were abolished (108 +/- 5%) 20 min after HS. Isotonic solution increased RBF and RVC in sham rats (149 +/- 10 and 145 +/- 12% of baseline, respectively, at 20 min). These responses were reduced in SAP rats (131 +/- 6 and 126 +/- 5%, respectively, at 20 min). Pressor responses to HS were larger in SAP rats than in sham rats (17 +/- 5 versus 9 +/- 2 mmHg, at 20 min), whereas during VE these responses were similar in both groups (6 +/- 3 versus 4 +/- 6 mmHg, at 20 min). Immunohistochemical analysis indicates that microinjections of anti-DbetaH-saporin produced extensive destruction within the A1/C1 cell groups in the CVLM. These results suggest that catecholaminergic neurones mediate the cardiovascular responses to VE or increases in plasma sodium levels.

Anteroventral third ventricle lesions impair cardiovascular responses to intravenous hypertonic saline infusion.

The anteroventral third ventricle (AV3V) region is a critical area of the forebrain, acting on fluid and electrolyte balance and maintaining cardiovascular homeostasis. The purpose of this study was to determine the effects of lesions to the anteroventral third ventricle region on cardiovascular responses to intravenous hypertonic saline (HS) infusion. Male Wistar rats were anesthetized with urethane. The femoral artery and jugular vein were cannulated to record mean arterial pressure (MAP) and infuse hypertonic saline (3M NaCl, 0.18 mL/100 g bw, over 1 min), respectively. Renal blood flow (RBF) was recorded by ultrasonic transit-time flow probes. Renal vascular conductance (RVC) was calculated as renal blood flow to mean arterial pressure ratio and expressed as percentage of baseline. After hypertonic saline infusion in sham animals, renal blood flow and renal vascular conductance increased to 137+10% and 125+7% (10 min), and 141+/-10% and 133+/-10% (60 min), respectively. Increases in mean arterial pressure (20-min peak: 12+/-3 mm Hg) were also observed. An acute lesion in the AV3V region (DC, 2 mA 25s) 30 min before infusion abrogated the effects of hypertonic saline. Mean arterial pressure was unchanged and renal blood flow and renal vascular conductance were 107+/-7% and 103+/-6% (10 min), and 107+/-4 and 106+/-4% (60 min), respectively. Marked tachycardia was observed immediately after lesion. Responses of chronic sham or lesioned rats were similar to those of acute animals. However, in chronic lesioned rats, hypertonic saline induced sustained hypertension. These results demonstrate that integrity of the AV3V region is essential for the renal vasodilation that follows acute changes in extracellular fluid compartment composition.

Sobre a regulaçäo do fluxo sangüíneo / Blood flow regulation

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