Perinatal development and adult blood pressure

A growing body of evidence supports the concept of fetal programming in cardiovascular disease in man, which asserts that an insult experienced in utero exerts a long-term influence on cardiovascular function, leading to disease in adulthood. However, this hypothesis is not universally accepted, hence animal models may be of value in determining potential physiological mechanisms which could explain how fetal undernutrition results in cardiovascular disease in later life. This review describes two major animal models of cardiovascular programming, the in utero protein-restricted rat and the cross-fostered spontaneously hypertensive rat. In the former model, moderate maternal protein restriction during pregnancy induces an increase in offspring blood pressure of 20-30 mmHg. This hypertensive effect is mediated, in part, by fetal exposure to excess maternal glucocorticoids as a result of a deficiency in placental 11-ß hydroxysteroid dehydrogenase type 2. Furthermore, nephrogenesis is impaired in this model which, coupled with increased activity of the renin-angiotensin system, could also contribute to the greater blood pressure displayed by these animals. The second model discussed is the cross-fostered spontaneously hypertensive rat. Spontaneously hypertensive rats develop severe hypertension without external intervention; however, their adult blood pressure may be lowered by 20-30 mmHg by cross-fostering pups to a normotensive dam within the first two weeks of lactation. The mechanisms responsible for this antihypertensive effect are less clear, but may also involve altered renal function and down-regulation of the renin-angiotensin system. These two models clearly show that adult blood pressure is influenced by exposure to one of a number of stimuli during critical stages of perinatal development.

Alterations in proteins of bone marrow extracellular matrix in undernourished mice

The objective of the present study was to determine the effect of protein malnutrition on the glycoprotein content of bone marrow extracellular matrix (ECM). Two-month-old male Swiss mice were submitted to protein malnutrition with a low-protein diet containing 4% casein as compared to 20% casein in the control diet. When the experimental group had attained a 20% loss of their original body weight, we extracted the ECM proteins from bone marrow with PBS buffer, and analyzed ECM samples by SDS-PAGE (7.5%) and ECL Western blotting. Quantitative differences were observed between control and experimental groups. Bone marrow ECM from undernourished mice had greater amounts of extractable fibronectin (1.6-fold increase) and laminin (4.8-fold increase) when compared to the control group. These results suggest an association between fluctuations in the composition of the hematopoietic microenvironment and altered hematopoiesis observed in undernourished mice.

Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished monkeys

Undernutrition elicited by a low-protein diet determines a marked reduction of hypophyseal activity and affects the function of the respective target organs. The objective of the present investigation was to study the ultrastructural and quantitative immunohistochemical changes of the different pituitary cell populations in undernourished monkeys that had been previously shown to have significant changes in craniofacial growth. Twenty Saimiri sciureus boliviensis monkeys of both sexes were used. The animals were born in captivity and were separated into two groups at one year of age, i.e., control and undernourished animals. The monkeys were fed ad libitum a 20% (control group) and a 10% (experimental group) protein diet for two years. Pituitaries were processed for light and electron microscopy. The former was immunolabeled with anti-GH, -PRL, -LH, -FSH, -ACTH, and -TSH sera. Volume density and cell density were measured using an image analyzer. Quantitative immunohistochemistry revealed a decrease in these parameters with regard to somatotrophs, lactotrophs, gonadotrophs and thyrotrophs from undernourished animals compared to control ones. In these populations, the ultrastructural study showed changes suggesting compensatory hyperfunction. On the contrary, no significant changes were found in the morphometric parameters or the ultrastructure of the corticotroph population. We conclude that in undernourished monkeys the somatotroph, lactotroph, gonadotroph, and thyrotroph cell populations showed quantitative immunohistochemical changes that can be correlated with ultrastructural findings.

Maternal undernutrition and the offspring kidney: from fetal to adult life

Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1R) or type 2 (AT2R) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1R is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2R expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na+/K+-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na+/K+-ATPase, leading to increased Na+ reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death.

Short Communication: effects of 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester on milk production and composition of lactating Holstein dairy cows

Sixteen multiparous Holstein cows were used to determine the effects of 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi: 0 vs. 1.26 g/kg of total ration dry matter (DM) and dietary crude protein (CP) concentration [14.7% (low) vs. 16.9% (standard), DM basis] on milk yield and composition using a replicated 4 x 4 Latin square design experiment with 4-wk periods. Cows were fed ad libitum a total mixed ration with a 1: 1 forage-to-concentrate ratio (DM basis), and diets provided an estimated 6.71 and 1.86% lysine and methionine, respectively, in metabolizable protein for the low-protein diet and 6.74 and 1.82% in the standard protein diet. Dry matter intake, milk yield, and composition were measured during wk 4 of each period. There were no effects on DM intake, which averaged 24.7 kg/d. There was an interaction between dietary CP and HMBi for milk yield and 3.5% fat-corrected milk (FCM). Feeding HMBi decreased milk and FCM yield when fed with the low-CP diet but did not affect milk or FCM yield when fed with the standard CP diet. Feeding HMBi increased milk protein concentration regardless of diet CP concentration and increased milk protein yield when added to the standard CP diet but not the low-CP diet. The positive effect of HMBi on milk protein yield was only observed at the standard level of dietary CP, suggesting other factors limited the response to HMBi when dietary protein supply was restricted.

Efeitos da dieta hipoprotéica na formação e composição de estruturas dentárias. Estudo Experimental em ratos wistar

Protein and caloric malnutrition has been considered one of the most concerned endemic diseases in Brazil and in the world. It has been known that depletion or reduction of proteins as far as meals are concerned can steer irreversible damages upon several organic systems. This study had as aim evaluate the effects the low-protein diet had over the formation and composition of the teeth components. 18 females and 6 males were used for the experiment. 12 from the 18 females had undertaken the low-protein diet (DH) for 03 weeks and the other 6, which remained, and those males had undertaken a controlled diet (DC) for the same period. All animals had the diets during their mating, pregnancy and lactation cycle. As soon as the offsprings had been born, 10 young males and females of each group faced a disease hood analysis to check the teeth germs of their lower fore teeth. The rest of the group had their lactation cycle normally 60 days. Then they were put to death and had their lower fore teeth removed both to be analyzed through a scanning electronic microscopy (SEM) of the structure alterations and to have their calcium checked by an atomic absorption of the phosphorus vanadate-molibdate method and by other minerals EDX method. The animals livers were removed to have their hepatic proteins analyzed as well. The histopatologic study showed that at first day of birth, all animals had their lower fore teeth come out. It was verified that 90% of the animals teeth were in an apposition and calcification period and it was possible to observe the dentin formation from 60% of the 90% already mentioned. Through the SEM method it could be realized that 90% of the animals of the DH group had their lower fore teeth easily broken and no definite shape. In this same group itself, it was also observed long micro fissures 369,66 nm ± 3,45 while the DC group had fissures of 174 nm ± 5,72. Now regarding the calcium and phosphorus concentration, it could be noticed that there was a great reduction of these components and other minerals in the DH group. Almost all minerals, except for the Cl and K, presented higher levels in the DC group enamel.The reduction of the protein input greatly influenced the offsprings´ weight and height. However the hepatic proteins had no important difference between the groups what can make one believe that those animals suffered from protein malnutrition of marasmic kind

Dietas de baixa proteína no desempenho de frangos criados em diferentes temperaturas

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

Descrição de dieta purificada para indução de quadro de desnutrição protéica em ratos

No presente trabalho é descrita a composição de dieta hipoprotéica (6% de proteína) purificada para indução de quadro de desnutrição em roedores. A referida dieta foi padronizada em laboratório a partir de modificação da AIN-93 (documento do American Institute of Nutrition que estabelece os padrões nutricionais para roedores de laboratório), visando a obtenção de animais desnutridos para estudar as alterações metabólicas decorrentes da desnutrição protéica associada a situações como exercício físico, gestação e diabetes. A dieta em questão contém os seguintes componentes (g/ kg): amido de milho (480), caseína (71,5), dextrina de milho (159), sacarose (121), óleo de soja (70), microcelulose (50), mistura mineral AIN-93-G-MX (35), mistura de vitaminas AIN-93-G-VX, (10), L-cistina (1), cloridrato de colina (2,5). Ratos alimentados cronicamente com a dieta apresentaram sinais comumente presentes na desnutrição protéica humana e de animais de laboratório: redução do ganho de peso, hipoproteinemia, hipoalbuminemia, elevação dos ácidos graxos livres séricos e do glicogênio hepático.

Dexamethasone treatment in vivo counteracts the functional pancreatic islet alterations caused by malnourishment in rats

The effects of dexamethasone (Dex) on the metabolic parameters, peripheral insulin, and glucose sensitivity in vivo as well as on islet function ex vivo of rats submitted to low-protein diet were analyzed. Dexamethasone (1.0 mg/kg body weight) was administered intraperitoneally daily to adult Wistar rats fed on a normal-protein diet or low-protein diet (LPD) for 5 days, whereas control rats fed on a normal-protein diet or low-protein diet (LP) received saline alone. At the end of the experimental period, LP rats showed a significant reduction in serum insulin, total serum protein, and serum albumin levels compared with rats fed on a normal-protein diet (P < .05). All these parameters tended to be normalized in LPD rats (P < .05); furthermore, these rats exhibited increased serum glucose and nonesterified fatty acid levels compared with LP rats (P < .05). Rats submitted to the low-protein diet demonstrated normal peripheral glucose sensitivity and improved peripheral insulin sensitivity, which was reversed by Dex treatment. A reduced area of islets from LP rats was partially recovered in LPD rats (P < .05). At 16.7 mmol/L glucose, insulin secretion from LPD islets was also partially recovered and was significantly higher than that from LP islets (P < .05). In conclusion, induction of insulin resistance by Dex treatment reverses most of the metabolic alterations in rats submitted to a low-protein diet. In addition, several islet functions were also improved by Dex, confirming the plasticity of pancreatic islets in adverse conditions. (C) 2008 Elsevier B.V. All rights reserved.

Female preferences based on male nutritional chemical traits

Selection favors females that attend to reliable information about male genetic quality and fitness. Male nutritional condition can be a significant sign of mate quality since poor nutrition can be related to reduced sperm quality, low sperm quantity, sexually transmitted diseases, and parasites. We tested whether female Nile tilapia, Oreochromis niloticus, preferred the chemical cues of males that were well fed with high-protein diet over those fed with low-protein diet. Females do not only discriminate between males but also show a preference for well-fed males, discriminating between the odors with respect to nutritional state, suggesting that they were responding to a food-specific chemical cue. It is therefore likely that nutritional condition is related to the production of pheromones in males. Our results suggest that information about male nutritional state can be conveyed in chemical cues and that females attend to these cues during mate choice.

The antiulcer effect of Croton cajucara Benth in normoproteic and malnourished rats

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

Maternal undernutrition and the offspring kidney: from fetal to adult life

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

Composição corporal e puberdade de leitoas alimentadas com níveis alto e baixo de proteína na dieta

Com o objetivo de verificar alterarações na composição corporal, diferentes níveis protéicos (12 e 18% PB) foram utilizados na dieta de leitoas de reposição, dos 100 aos 221 dias de idade. Durante esse período foram avaliados o peso corporal, espessura de toucinho (ET), manifestação de estro, características do trato reprodutivo e o balanço nitrogenado. Para a determinação do balanço nitrogenado, as leitoas foram submetidas a dois ensaios de digestibilidade (aos 136 e aos 201 dias de idade). em ambos os ensaios, as leitoas alimentadas com 18% PB apresentaram maior ingestão, retenção e excreção de nitrogênio e maiores níveis de uréia plasmática e urinária (P<0,001). A eficiência da utilização de nitrogênio não foi influenciada pelo nível protéico da dieta (P>0,05). Houve redução de 48% na excreção de nitrogênio com a dieta menos protéica. Leitoas alimentadas com 12% PB apresentaram maior ganho de ET (7,4 mm) em comparação às alimentadas com 18% PB (4,5 mm), dos 100 aos 207 dias de idade (P<0,02). O peso corporal, peso do útero, comprimento dos cornos uterinos e número de corpos lúteos não foram afetados pelo nível de proteína na dieta. A taxa de detecção de estro, até 25 dias após a exposição das leitoas ao cachaço, foi semelhante para as fêmeas recebendo 12% (71%) e 18% PB (75%). Os níveis de proteína da dieta afetaram a composição corporal das fêmeas sem que o peso final, o desencadeamento da puberdade e características do trato reprodutivo fossem afetados, indicando que dietas de baixa proteína podem ser utilizadas como estratégia para aumentar a espessura de toucinho de leitoas de reposição.

Leucine Supplementation Augments Insulin Secretion in Pancreatic Islets of Malnourished Mice

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

Caracterização morfológica, expressão dos fatores de regulação miogênica (MRFS) e dos receptores nicotínicos (NACHRS) no músculo estriado de ratos submetidos à restrição protéica materna

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