Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine

2002 ◽  
Vol 103 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Alan A. JACKSON ◽  
Rebecca L. DUNN ◽  
Michael C. MARCHAND ◽  
Simon C. LANGLEY-EVANS

When rat dams consume a diet low in protein during pregnancy, their offspring develop high blood pressure. On a low-protein diet, the endogenous formation of the amino acid glycine is thought to become constrained. Glycine may become conditionally essential, as its rate of endogenous formation is inadequate to meet metabolic needs, and may be limiting for the normal development of the fetus. In the present study, five groups of Wistar rats were provided during pregnancy with one of five diets: a control diet containing 18% (w/w) casein (CON), a low-protein diet containing 9% casein (MLP), or the low-protein diet supplemented with 3% glycine (MLPG), alanine (MLPA) or urea (MLPU). The offspring were weaned on to standard laboratory chow, and blood pressure was measured at 4 weeks of age. Blood pressure was significantly increased in the MLP, MLPA and MLPU groups compared with the CON group, but for the MLPG group blood pressure was not significantly different from CON. Compared with the CON group, body weight was significantly reduced for the MLP, MLPA and MLPG groups, but for the MLPU group body weight was not different from CON. These data show that different forms of non-essential dietary nitrogen, when consumed during pregnancy, exert different effects upon the growth and function of the offspring. The availability of glycine appears to be of critical importance for normal cardiovascular development.

1996 ◽  
Vol 91 (5) ◽  
pp. 607-615 ◽  
Author(s):  
Simon C. Langley-Evans ◽  
Simon J. M. Welham ◽  
Rachel C. Sherman ◽  
Alan A. Jackson

1. In the rat, hypertension is induced by fetal exposure to maternal low-protein diets. The effect on blood pressure of undernutrition before conception and during discrete periods in early, mid or late pregnancy was assessed using an 18% casein (control) diet and a 9% casein diet to apply mild protein restriction. 2. The offspring of rats fed 9% casein developed raised blood pressure by weaning age. Feeding a low-protein diet before conception was not a prerequisite for programming of hypertension. 3. Hypertension was observed in rats exposed to low protein during the following gestational periods: days 0–7, days 8–14 and days 15–22. Blood pressure increases elicited by these discrete periods of undernutrition were lower than those induced by feeding a low-protein diet throughout pregnancy. The effect in early gestation was significant only in male animals. Post-natal growth of male rats exposed to low-protein diets was accelerated, but kidneys were small in relation to body weight. 4. Biochemical indices of glucocorticoid action in liver, hippocampus, hypothalamus and lung were elevated in rats exposed to low-protein diets in utero. The apparent hypersensitivity to glucocorticoids was primarily associated with undernutrition in mid to late gestation. 5. Plasma renin activity was elevated in rats exposed to 9% casein over days 15–22 of gestation. Animals undernourished over days 0–7 and 8–14 produced pups with lower plasma angiotensin II concentrations at weaning. 6. Fetal exposure to maternal low-protein diets for any period in gestation may programme hypertension in the rat. Alterations to renal structure, renal hormone action or the hypothalamic—pituitary-adrenal axis may all play a role in the programming phenomenon, either independently or in concert.


2000 ◽  
Vol 98 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Rachel C. SHERMAN ◽  
Simon C. LANGLEY-EVANS

Epidemiological evidence from diverse human populations, supported by experimental evidence from animal models, suggests that maternal nutrition during pregnancy is an important fetal programming influence upon cardiovascular disease. Experiments with a low-protein-diet model of rat pregnancy suggest a role for the renin–angiotensin system in the programming mechanism, since fetal undernutrition permanently elevates pulmonary and plasma angiotensin-converting enzyme activity. Long-term beneficial effects of captopril on blood pressure in this model require further investigation in order to clarify the role of angiotensin II. Pregnant rats were fed a control diet containing 18% (w/w) casein as the protein source or a low-protein diet containing 9% (w/w) casein. Between the ages of 2 and 4 weeks postnatally, mothers and their pups were treated with losartan or nifedipine. All pups in the study had blood pressure determined at 4 and 12 weeks of age using a tail cuff. Animals exposed to the low-protein diet in utero and not subjected to drug treatment had elevated blood pressure relative to control rats (mean increase of 27 mmHg; P < 0.001). Treatment of rats exposed to the control diet in utero with either nifedipine or losartan between 2 and 4 weeks of age did not alter their blood pressure. Nifedipine had no effect upon the blood pressure of low-protein-exposed pups, but losartan prevented the blood pressure elevation in these animals. Between 4 and 12 weeks of age, blood pressure increased significantly in all groups (P < 0.001). The pattern of blood pressure among the groups was identical to that observed at 4 weeks, suggesting that the observed early effects of losartan would be maintained into adult life. The data are consistent with the hypothesis that angiotensin II plays a major role in the prenatal programming of hypertension. The action of angiotensin II at the AT1 receptor between 2 and 4 weeks of age may be critically up-regulated by fetal factors, including exposure to glucocorticoids of maternal origin.


1973 ◽  
Vol 45 (s1) ◽  
pp. 99s-102s
Author(s):  
Hideo Ueda

1. High-salt, high-carbohydrate and low-protein diet induces remarkable elevation of blood pressure in spontaneous hypertensive rats (SHR). 2. These animals have low serum potassium, low blood urea nitrogen and high blood sugar. 3. Heart weight is increased in proportion to the elevation of blood pressure. 4. Kidney weight of rats receiving the high-salt, high-carbohydrate and low-protein diet was, by contrast, smaller than SHR receiving a normal diet. 5. The kidneys of SHR receiving a high-salt, high-protein diet were twice as heavy as the kidneys of normal rats. 6. Similar dietary modifications in Goldblatt hypertensive rats to those in SHR produced similar changes in blood pressure and heart weight.


2002 ◽  
Vol 87 (2) ◽  
pp. 147-155 ◽  
Author(s):  
Francisco B. Barbosa ◽  
Kirsten Capito ◽  
Hans Kofod ◽  
Peter Thams

Pancreatic islets were isolated from rats that had been nursed by dams fed with a control or an 8·7 % protein diet during the first 12 d of the lactation period. Glucose-induced insulin secretion from islets in the 8·7 % protein group was reduced 50 %. The islet insulin and DNA content were similar, whereas the pancreatic insulin content was reduced by 30 % in the rats fed 8·7 % protein. In order to elucidate the mechanism responsible for the attenuation of insulin secretion, measurements were performed of the activity of several islet enzymes that had previously been supposed to be involved in the coupling of glucose stimulation to insulin secretion. Islet glucose oxidation was unaffected, but glucose-stimulated hydrolysis of phosphatidylinositol was reduced by one-third in the islets of rats fed 8·7 % protein. The activity of mitochondrial glycerophosphate dehydrogenase was similar in islets of rats fed the 8·7 % protein diet and those fed the control diet. The activity of Ca-independent phospholipase A2was increased fourfold in the islets of rats fed 8·7 % protein. It is concluded that impairment of glucose-induced insulin secretion in rats fed a low-protein diet may be caused by attenuation of islet phosphatidylinositol hydrolysis, and it is tentatively suggested that the increased activity of Ca-independent phospholipase A2in islets of rats fed a low-protein diet may participate in the stimulation of apoptosis.


2016 ◽  
Vol 8 (2) ◽  
pp. 178-187 ◽  
Author(s):  
E. Matsumoto ◽  
S. Kataoka ◽  
Y. Mukai ◽  
M. Sato ◽  
S. Sato

Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0.12% GTE-containing low-protein diet during lactation (LPL), and low-protein diet during gestation and 0.24% GTE-containing low-protein diet during lactation (LPH). The female offspring were sacrificed at day 22. Biochemical parameters in the plasma, macrophage infiltration, degree of fibrosis and expression levels of AMPK and Akt were examined. The plasma insulin level increased in LPH compared with LPC. Percentage of the fibrotic areas and the number of macrophages in LPC were higher than those in CC. Conversely, the fibrotic areas and the macrophage number in LPH were smaller (21 and 56%, respectively) than those in LPC. The levels of phosphorylated AMPK in LPL and LPH, and Akt in LPH were greater than those in LPC. In conclusion, maternal protein restriction may induce macrophage infiltration and the decrease of insulin levels. However, GTE intake during lactation may suppress macrophage infiltration and restore insulin secretion function via upregulation of AMPK and insulin signaling in weanlings.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Daniel Tomé ◽  
Joanna Moro ◽  
Anne Blais ◽  
Catherine Chaumontet ◽  
Patrick Even ◽  
...  

Abstract Objectives Low protein diet and essential amino acid deficient-diet have an impact on body weight and growth and different studies also showed an impact of lysine intake on bone metabolism. Lysine has been shown to promote the absorption of intestinal calcium and to participate in the collagen synthesis through its involvement in the reticulation process of the tropocollagen beams. The assembly of tropocollagen bundle into mature collagen fibers is essential for bone formation and remodeling (civitelli et al, 1992; Fini et al, 2001). The objective of this study was to characterize the impact of low protein diet and lysine-deficient diet on bone metabolism of growing rats. Methods Study 1: 6 group of growing rats were fed for 3 weeks different diet with different content of milk protein at levels of 3%, 5%, 8%, 12%, 15% or 20% (% total energy). Study 2: 7 group of growing rats were fed diets with different lysine content (as % of lysine requirement), for 3 weeks: 15%, 25%, 40%, 60%, 75%, 100% or 170% (% Lysine requirement). Body weight was measured daily. At the end of the experiment, the body composition was analyzed and tissues were removed for measurements of the expression of genes involved in protein and bone metabolism. Statistical analysis was done by variance analysis. Results Rats fed low protein diet (3% and 5% of milk protein), compared to control have a lower growth, with a lower body weight and naso-anal length. This weak growth was associated with a lower lean body mass, and also had an impact on bone metabolism. There was a decrease in the bone mineral density, bone mineral content and femur size, associated with a decrease of markers of bone turnover and formation. The same results on bone metabolism were observed on rats fed the 85% lysine deficient diet. Conclusions Low protein diet and lysine-deficient diet reduce growth and bone metabolism. The impact of low protein diet could be related to the lysine deficiency, which have an impact on the calcium intestinal absorption and on collagen synthesis. Funding Sources INRA, AgroParisTech. Supporting Tables, Images and/or Graphs


1996 ◽  
Vol 270 (6) ◽  
pp. R1189-R1196 ◽  
Author(s):  
A. Okiyama ◽  
K. Torii ◽  
M. G. Tordoff

Four studies were conducted to assess the effect of a low-protein diet on NaCl intake. Young rats fed either control (20% casein) or low-protein (5% casein) high-carbohydrate (CHO) diet were allowed to drink either water alone or water and 300 mM NaCl. Relative to rats fed control diet, rats fed the low-protein diet progressively increased NaCl intake so that, despite lower food and water intakes, they drank 180% more NaCl during the last 3 days of the 21-day test. Additional studies found that rats fed low-protein diet always maintained positive sodium balance, were neither sodium depleted nor hypovolemic, and had normal plasma renin activity and aldosterone concentrations. The elevated NaCl intake was not secondary to calcium deficiency and was unaffected by mineral supplementation of the protein-deficient diet. Increases in the diet's CH and/or fat content incidental to decreases in its protein content influenced, but could not completely account for, the effect of protein deficiency on NaCl intake. We conclude that protein deficiency is the primary cause of the elevated NaCl preference produced by being fed a low-protein diet and that a novel physiological mechanism underlies this behavior.


2002 ◽  
Vol 283 (3) ◽  
pp. R623-R630 ◽  
Author(s):  
Eric Bertin ◽  
Marie-Noëlle Gangnerau ◽  
Georges Bellon ◽  
Danièle Bailbé ◽  
Annick Arbelot De Vacqueur ◽  
...  

Fetal malnutrition is now proposed as a risk factor of later obesity and type II diabetes. We previously analyzed the long-term impact of reduced protein and/or energy intake strictly limited to the last week of pregnancy in Wistar rats. Three protocols of gestational malnutrition were used: 1) low-protein isocaloric diet (5 instead of 15%) with pair feeding to the mothers receiving the control diet, 2) restricted diet (50% of control diet), and 3) low protein-restricted diet (50% of low-protein diet). Only isolated protein restriction induced a long-term β-cell mass decrease. In the present study, we used the same protocols of food restriction to analyze their short-term impact (on day 21.5 of pregnancy) on β-cell mass development. A 50% β-cell mass decrease was present in the three restricted groups, but low-protein diet, either associated or not to energy restriction, increased fetal β-cell insulin content. Among all the parameters analyzed to further explain our results, we found that the fetal plasma level of taurine was lowered by low-protein diet and was the main predictor of the fetal plasma insulin level ( r = 0.63, P < 0.01). In conclusion, rat fetuses exposed to protein and/or energy restriction during the third part of pregnancy have a similar dramatic decrease in β-cell mass, and their ability to recover β-cell mass development retardation depends on the type of malnutrition used. Moreover, our results support the hypothesis that taurine might play an important role in fetal β-cell mass function.


1980 ◽  
Vol 94 (3) ◽  
pp. 321-326 ◽  
Author(s):  
Kazue Takano ◽  
Naomi Hizuka ◽  
Kazuo Shizume ◽  
Yoko Hasumi ◽  
Toshio Tsushima

Abstract. Serum somatomedin A was significantly reduced after 3 days of fasting in rats with a mean decrease of 23.6 ± 2.4% (N = 18) of initial values. Re-feeding for one day produced a definite increase in somatomedin A, with a rise in body weight. When re-fed isocalorically for 21 days with diets of different quality, a low protein diet led to smaller increases in both seum somatomedin A and body weight in comparison to those of control-, high-protein- and high fat-diets (P < 0.001). There is a positive correlation between the increase in body weight and serum somatomedin A levels (N = 70, r = 0.71, P< 0.001). The effect of growth hormone on somatomedin generation was abolished in hypophysectomized rats fed with low-protein diet. Our study suggests that protein in the diet is important for the generation of somatomedin A, which is necessary for normal growth.


1966 ◽  
Vol 44 (6) ◽  
pp. 809-817 ◽  
Author(s):  
Sheila I. Read ◽  
E. J. Middleton ◽  
W. P. Mckinley

Female rats were fed diets low in minerals, vitamins, or protein, or a control diet, both alone and supplemented with 10 parts per million (p.p.m.) parathion for 3 weeks. Male and female rats were fed control and tow-vitamin diets both with and without parathion supplementation (0–10 p.p.m.) for 3 weeks. The liver and kidney carboxylesterases (EC 3.1.1.1.), and the plasma acetylcholinesterases (EC 3.1.1.7.) of the male rats, were measured.In the female rats, a low-mineral diet resulted in an increase of carboxylesterases in the liver and kidney; a low-vitamin diet caused a marked increase in liver carboxylesterases but had no effect on the carboxylesterases of the kidney. Parathion at 10 p.p.m. in all diets greatly reduced the liver carboxylesterases but had less effect on kidney carboxylesterases, except in the case of the low-protein diet, for which the reduction was similar to that in the liver. Varying amounts of parathion added to the low-vitamin diet reduced the liver and kidney carboxylesterases, but to a less extent than when added to the control diet.The liver carboxylesterases of male rats were inhibited approximately 50% by 2 p.p.m. parathion in the control diet and by 4 p.p.m. parathion in the low-vitamin diet. However, inhibition of plasma acetylcholinesterase and kidney carboxylesterases was not marked until the 10 p.p.m. parathion level was fed. The acetylcholinesterase activity of the plasma of male rats did not decrease until the level of liver carboxylesterases was very low.


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