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.

Epidemiological evidence shows that small size at birth is associated with an increased risk of developing cardiovascular and metabolic disease in adult life. We have examined the relationships between size at birth and maternal body composition and protein turnover in normal pregnant women. A group of 27 multiparous Caucasian women with singleton pregnancies were studied at around 18 and 28 weeks' gestation. Body composition was determined by anthropometry, and whole-body protein turnover was estimated by using a single oral dose of [ 15 N]glycine and the end-product method. The baby's weight and length were measured within 48 h of birth. Mothers with a greater lean body mass had higher rates of protein turnover at 18 weeks' gestation. This association was largely accounted for by differences in the mother's visceral, rather than muscle, mass. Mothers who had higher protein turnover at 18 weeks' gestation had babies that were longer at birth. After adjustment for the duration of gestation and the baby's sex, 26% of the variation in length at birth was accounted for by maternal protein synthesis at 18 weeks' gestation. Maternal protein intake was not associated with the baby's birth length. Thus the mother's ability to nourish her fetus is influenced by her body composition and her rate of protein turnover. Dietary intake does not adequately characterize this ability.

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.

1. Urea kinetics were measured in six healthy men using prime/intermittent oral doses of [ 15 N 15 N] urea, after five days consuming one of four diets which varied in their nitrogen content: a reference diet (REF, 70 g of protein and 11.2 g of N); a low-protein diet (LP, 30 g of protein and 4.8 g of N); a low-protein diet with 6.9 g of urea added (LP-U1, 30 g of protein and 8 g of N); a low-protein diet with 13.7 g of urea added (LP-U2, 30 g of protein and 11.2 g of N). 2. Apparent nitrogen balance on the REF diet was significantly better than on the LP or the LP-U1 diets. The addition of the higher level of urea in the LP-U2 diet enhanced apparent nitrogen balance compared with the LP or LP-U1 diets, and was not different to apparent nitrogen balance on the REF diet. 3. On the LP, LP-U1 and LP-U2 diets, the rate of endogenous urea production was not different, and was about 60% of that on the REF diet, a statistically significant difference. The addition of a dietary supplement of urea increased the rate of urea appearance in the urea pool in direct relation to the dose of urea taken. There was no difference in the rate of appearance between the REF and LP-U2 diets, for both of which the rate of appearance was significantly greater than on the LP diet. 4. The excretion of urea in urine on the LP diet was 62% of that on the REF diet, a significant difference. There was no significant difference in the rate of urea excretion between the REF, LP-U1 and LP-U2 diets. 5. The rate of urea hydrolysis by the colonic microflora on the REF diet was more than twice that on the LP or LP-U1 diets. Supplementation with urea at the higher level, LP-U2, significantly increased hydrolysis to the same level as on the REF diet. Most of the nitrogen derived from urea hydrolysis was retained in the metabolic pool (>80%), with no difference in the rate of retention between the REF and LP-U2 diets, both greater than the LP or LP-U1 diets. 6. The dietary supplements of urea increased the size of the body urea pool significantly. Renal clearance of urea was highest on the REF diet and decreased 13–29% on the low-protein diets. Bowel clearance was highest on the REF diet and decreased 46–55% on the low-protein diets. Neither urinary excretion of urea nor urea hydrolysis in the bowel were related simply to the concentration of urea in blood. Urea hydrolysis related most closely to the rate of appearance of urea in the urea pool. 7. The salvage of urea nitrogen was increased on the highest level of supplementation, but the overall sensitivity of the system was low, suggesting that other factors might be limiting for effective urea hydrolysis and the salvage of urea nitrogen.

1. Possible associations between maternal nutrition in pregnancy and non-communicable diseases of adulthood were assessed using a rat model. Rats were habituated to diets containing a range of protein levels (18, 12, 9 and 6% by weight), over a 14 day period, before mating. The low protein diets were maintained throughout pregnancy. Lactating mothers and their offspring were transferred to a standard chow diet (20% protein). 2. Pregnant rats demonstrated a graded response to the diets, with those fed 9 and 6% protein tending to consume less energy and gain less weight than 18% protein fed controls. Litter size and newborn death rates were not significantly altered by the low protein diets. 3. Offspring of 12 and 9% protein fed dams were grossly normal, gaining weight at a similar rate to those born to 18% protein fed control rats. Offspring of the 6% protein fed dams were smaller than pups from all other groups, over a 21 week period. 4. At 9 weeks of age, systolic blood pressure was determined in the offspring. All offspring from the three low protein groups were found to have significantly elevated blood pressure (15–22 mmHg) relative to the control group. An inverse relationship between maternal protein intake and the systolic blood pressure of the offspring was observed. Blood pressure remained elevated in the offspring of the 9 and 6% protein fed dams until 21 weeks of age. The observed hypertension was associated with increased pulmonary angiotensin-converting enzyme activity in the low protein groups. 5. The data are consistent with the hypothesis that poor maternal nutrition in pregnancy may irreversibly impair aspects of physiological and biochemical function in the fetus. This has potential adverse consequences for the later health of the offspring.

1. Whole body protein turnover and resting metabolic rate were measured in six adults with homozygous sickle cell disease (genotype HbSS ) and in six normal adults (genotype HbAA ) of similar age. 2. Turnover was measured with prime/intermittent oral doses of [ 15 N]glycine over 18 h and resting energy expenditure was measured by indirect calorimetry. 3. In HbSS , nitrogen flux (0.9 ± 0.08 g day −1 kg −1 ), protein synthesis (6.0 ± 0.5 g day −1 kg −1 ) and protein degradation (5.6 ± 0.5 g day −1 kg −1 ) were significantly increased compared with HbAA nitrogen (flux 0.5 ± 0.02 g day −1 kg −1 , protein synthesis 3.2 ± 0.2 g day −1 kg −1 and protein degradation 2.8 ± 0.2 g day −1 kg −1 ). 4. Resting energy expenditure was significantly higher in HbSS compared with HbAA when expressed per unit of body weight (115 ± 3 and 94 ± 4 kJ day −1 kg −1 , respectively) or weight 0.75 (317 ± 6 and 269 ± 8 kJ day −1 kg −0.75 , respectively). 5. The increase in protein turnover and energy expenditure suggest that patients with HbSS exist in a hypermetabolic state that requires greater dietary energy compared with HbAA .