Metabolic Programming during Lactation Stimulates Renal Na+ Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways

BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood

Prevenção da síndrome metabólica em crianças obesas: uma proposta de intervenção Prevención del síndrome metabólico en niños obesos: una propuesta de intervención Prevention of metabolic syndrome in obese children: a proposal of intervention

OBJETIVO: Analisar o efeito de 12 semanas de intervenção envolvendo prática de atividade física, orientações alimentar e psicológica sobre fatores de risco para o desenvolvimento da síndrome metabólica em crianças e adolescentes obesos. MÉTODOS: Estudo longitudinal com 23 crianças e adolescentes obesos, com idade entre seis e 16 anos (12,0±3,2 anos). Foram mensurados: gordura corporal total e de tronco, glicemia, colesterol total e triglicérides, pressão arterial sistólica e diastólica. Os jovens foram submetidos a três sessões semanais de 60 minutos de exercício físico (atividades esportivas recreativas, ginástica, circuitos e caminhadas), durante 12 semanas. O teste do qui-quadrado foi usado para comparar dados categóricos daqueles que apresentaram valores acima das recomendações para cada fator de risco. O teste t para dados pareados foi aplicado para comparar os dois momentos do estudo. RESULTADOS: Em indivíduos com alterações metabólicas no início do estudo, observou-se, após a intervenção, a diminuição de 11,6% na glicemia (105 para 93mg/dL; p=0,046) e de 24,9% no triglicérides (217 para 163mg/dL; p=0,013); porém, não houve diferenças na pressão arterial e no colesterol total. CONCLUSÕES: O programa de exercício físico aplicado nas crianças e adolescentes foi eficiente para melhorar os valores de glicemia e triglicérides.<br>OBJETIVO: Analizar el efecto de 12 semanas de intervención implicando práctica de actividad física, orientación alimentar y psicológica sobre factores de riesgo respecto al desarrollo del síndrome metabólico en niños y adolescentes obesos. MÉTODOS: Estudio longitudinal con 23 niños y adolescentes obsesos, con edad entre seis y 16 años (12,0±3,2 años). Se midió: grasa corporal total y de tronco, glucemia, colesterol total y triglicéridos, presión arterial sistólica y diastólica Los jóvenes fueron sometidos a tres sesiones semanales de 60 minutos de ejercicio físico (actividades deportivas recreativas, gimnástica, circuitos y caminatas) durante 12 semanas. En el tratamiento estadístico, se realizó el análisis descriptivo, con promedio, desviación estándar y error estándar. La prueba de chi cuadrado fue usada para comparar datos categóricos con aquellos que presentaron valores por encima de las recomendaciones para cada Factor de Riesgo y la prueba t para datos pareados fue usada para comparar los dos momentos del estudio. RESULTADOS: En individuos con alteraciones metabólicas en el inicio del estudio, se observó, después de la intervención, reducción del 11,6% en la glucemia (1053mg/dL para 93mg/dL; p=0,046) y del 24,9% en los triglicéridos (217mg/dL para 163mg/dL; p=0,013); sin embargo, no hubo diferencias en la presión arterial y en el colesterol total. CONCLUSIÓN: El programa de ejercicio físico aplicado en los niños y adolescentes fue eficiente para mejorar los valores de glucemia y triglicéridos.<br>OBJECTIVE: To analyze the effects of a 12-week intervention program based on physical activity practice, alimentary and psychological orientation on the risk factors for the development of metabolic syndrome in obese children and adolescents. METHODS: A longitudinal study was conducted with 23 obese children and adolescents, aged six to 16 years (12.0±3.2 years). Total body and trunk fat mass, glycemia, total cholesterol, triglycerides, systolic and diastolic blood pressure were measured. The children were submitted to physical activity three times a week during 12 weeks. Each session of 60 minutes consisted of recreational sports activities, gymnastics, circuits and track-walking. Chi-square test was used to compare categorical data for those patients who had values above the recommendations for each risk factor and Student's t-test for paired data was used to compare the two moments of the study. RESULTS: In subjects who had altered baseline values in the beginning of the study, the glycemia levels decreased 11.6% (from 105 to 93mg/dL; p=0.046) and the triglycerides decreased 24.9% (from 217 to 163mg/dL; p=0.013) after the intervention. On the other hand, no differences were noted for blood pressure and total cholesterol after the intervention. CCONCLUSIONS: The intervention was effective in improving blood glucose and triglycerides levels in children and adolescents enrolled in the study

The effect of saponins from <it>Ampelozizyphus amazonicus</it> Ducke on the renal Na⁺ pumps’ activities and urinary excretion of natriuretic peptides

<p>Abstract</p> <p>Background</p> <p>In a previous study, we showed that a saponin mixture isolated from the roots of <it>Ampelozizyphus amazonicus</it> Ducke (SAP<it>Aa</it>D) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAP<it>Aa</it>D- induced antidiuresis in rats.</p> <p>Methods</p> <p>To evaluate the effect of SAP<it>Aa</it>D on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAP<it>Aa</it>D (<it>SAPAaD + Furo</it>) or 0.5 ml of 0.9 % NaCl (<it>NaCl + Furo</it>). In the <it>SAPAaD + NaCl</it> group, rats were pretreated with SAP<it>Aa</it>D and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na⁺ pumps on antidiuretic effects promoted by SAP<it>Aa</it>D, rats were given the physiological solution (as above) containing SAP<it>Aa</it>D (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na⁺- and (Na⁺,K⁺)-ATPases were calculated from the difference between the [³²P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively.</p> <p>Results</p> <p>It was observed that SAP<it>Aa</it>D inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, <it>NaCl + Furo</it> group, n = 5, to 5.9 ± 1.0 mL, <it>SAPAaD + Furo</it> group n = 5, p < 0.05), increased both Na⁺-ATPase (from 25.0 ± 5.9 nmol Pi.mg^-1.min^-1, control, to 52.7 ± 8.9 nmol Pi.mg^-1.min^-1, p < 0.05) and (Na⁺,K⁺)-ATPase (from 47.8 ± 13.3 nmol Pi.mg^-1.min^-1, control, to 79.8 ± 6.9 nmol Pi .mg^-1.min^-1, p < 0.05) activities in the renal cortex. SAP<it>Aa</it>D also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP.</p> <p>Conclusion</p> <p>We concluded that the SAP<it>Aa</it>D antidiuretic effect may be due to an increase in the renal activities of Na⁺- and (Na⁺,K⁺)-ATPases and/or a decrease in the renal ANP.</p