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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The feeding of low protein diets to pregnant rats is known to programme hypertension in their offspring though a glucocorticoid-dependent mechanism. To establish whether diets of differing fatty acid composition could produce the same effects, or modulate the effects of a low protein diet, pregnant rats were fed 1 of 4 different diets. Control animals were fed an 18% casein:corn oil (18 + Corn) diet, while experimental groups were fed 18% casein:coconut oil (18 + Coco), 9% casein:corn oil (9 + Corn) or 9% casein:coconut oil (9 + Coco). Feeding of coconut oil diets significantly reduced weight gain of the rats, an effect attributable to a lower food intake. Despite this, reproductive performance of the rats was not compromised. While pups of the 9 + Corn group were of normal birthweight, the dams in the 18 + Coco and 9 + Coco groups gave birth to pups of significantly lower weight. At 7 weeks of age male and female pups exposed to the 9 + Corn diet in utero had significantly elevated systolic blood pressure. Males exposed to the 9 + Coco and 18 + Coco diets also had higher blood pressures than control animals, but the effect was not observed in females. Female rats exposed to the three experimental diets in utero had enlarged hearts, relative to controls and the same effect of maternal diet was observed in male rats exposed to the 9 + Coco and 18 + Coco diets. Effects of maternal diet upon liver size were also noted in males exposed to 18 + Coco and 9 + Corn diets (smaller livers). Males exposed to 9 + Corn had smaller lungs than control rats, whilst the rats from the 9 + Coco group had significantly enlarged lungs. In rats exposed to the 9 + Corn diet in utero there was evidence of increased glucocorticoid action in both liver and hypothalamus, where activities of corticosteroid inducible enzymes were elevated. There was no evidence of a role for glucocorticoids in programming the hypertension of male rats exposed to high saturated fat diets in utero. The data would suggest that high saturated fatty acid, or low linoleic acid intake in pregnancy may programme hypertension in the fetal rat. This effect of maternal diet occurs through a mechanism different to that initiated by protein restriction and is sex specific.
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PMID:Intrauterine programming of hypertension in the rat: nutrient interactions. 875 81

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 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 15-55 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.
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PMID:Weanling rats exposed to maternal low-protein diets during discrete periods of gestation exhibit differing severity of hypertension. 894

Spontaneously hypertensive 4-week-old male rats were fed, before and after the onset of hypertension, with either commercial chow (control) or commercial chow combined with different forms of milk proteins with or without calcium supplementation. After 40 weeks, rats were still hypertensive, and dopamine-beta-hydroxylase enzyme activity measured simultaneously in serum and adrenal was found to be higher than in the controls. The enzyme activity in rats fed diets with milk proteins was increased significantly in both serum and adrenal compared with the control, and such enhancement was significantly higher than that observed in animals fed the commercial diet supplemented with calcium (1.2%), suggesting that dietary calcium intake associated with dietary protein of high digestibility, such as casein, potentiates the endogenous mechanisms regulating the homeostasis of calcium more than calcium supplementation itself. Moreover, the selective and additive effect of diets supplemented with milk proteins and calcium on adrenal enzyme activity clearly suggests a relationship between cardiovascular diseases involving the genesis of hypertension and stress mechanisms through the hypothalamo-pituitary adreno-sympathetic axis.
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PMID:Dietary calcium supplementation and dopamine-beta-hydroxylase in spontaneously hypertensive rats. 925 61

Recent epidemiological evidence suggests that adult cardiovascular risk is determined by birth weight and factors that influence birth weight, such as maternal nutrition. Data from animal models suggest that an interaction between nutrition and glucocorticoid hormones "programs" increased risk of adult hypertension. Increased fetal exposure to maternal glucocorticoids that is proposed to occur from a reduction in the placental barrier to maternal glucocorticoid, 11beta-hydroxysteroid dehydrogenase, is suggested to program hypertension in the resultant offspring from both glucocorticoid-treated and maternally protein-restricted rats. The extent to which postnatal glucocorticoid stimulation may influence the progression of hypertension in the offspring from protein-restricted rat dams was assessed in 6-week-old male Wistar rats, prenatally exposed to either an 18% casein (control) or 9% casein (low protein) diet. Rats from each dietary group were sham operated, adrenalectomized or adrenalectomized, and treated with 20 mg corticosterone/kg body weight per day. Before surgery, systolic blood pressure was significantly higher in the low protein-exposed rats compared with controls (165+/-3.8 versus 142+/-3.3 mm Hg, P<.0001). Adrenalectomy of the low protein-exposed animals significantly reduced the blood pressure to control levels, while corticosterone replacement restored the hypertensive state. No effect of adrenalectomy on blood pressure was observed in 18% casein controls. In both dietary groups adrenalectomy decreased brain, but not hepatic, glucocorticoid-sensitive enzyme activities and corticosterone treatment elevated activities of all enzymes. The data suggest that maternal diet-induced hypertension is dependent on an intact adrenal gland postnatally and that glucocorticoids are key trophic agents in maintaining the high blood pressure.
Hypertension 1997 Dec
PMID:Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids. 940 77

1. In the rat low birthweight and raised systolic blood pressure are the consequence of fetal exposure to maternal low protein diets. Nutritional down-regulation of the placental isoform of 11 beta-hydroxysteroid dehydrogenase, which may increase exposure of the fetus to maternal glucocorticoids, has been suggested to underlie effects of low protein diets on fetal growth and blood pressure. 2. Pregnant rats were fed control (18% casein) or low protein (9% casein) diets throughout gestation. Animals fed the control diet were injected with carbenoxolone, an inhibitor of 11 beta-hydroxysteroid dehydrogenase. Injections were administered either throughout pregnancy (day 0-22), or targeted to specific periods in early (days 0-7), mid- (days 8-14) or late (days 15-22) gestation. 3. Exposure to a low protein diet reduced birthweight and at 4 weeks of age systolic blood pressure was significantly elevated in the rats exposed to low protein. These hypertensive animals had small kidneys in proportion to body weight. 4. Fetal exposure to carbenoxolone at any period in gestation resulted in lower weight at birth. In rats exposed to the inhibitor over days 8-14, 15-22 or 0-22 systolic blood pressure at 4 weeks was significantly higher than in control animals. The greatest elevation of pressure was associated with carbenoxolone treatment in late (days 15-22) gestation. Animals with carbenoxolone-induced hypertension did not exhibit evidence of retarded renal growth. 5. Increased fetal exposure to maternal glucocorticoids impairs fetal growth and programmes elevated blood pressure in later life.
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PMID:Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. 948 87

1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of 'programmed' hypertension was used to investigate the role of the renin-angiotensin system in the initiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24-25 mmHg higher than those of rats exposed to a control diet in utero. 4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg. 5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopril-treated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero. 6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals.
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PMID:Early administration of angiotensin-converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low-protein diet in the rat. 964 Mar 37

A link between prenatal malnutrition and hypertension in human populations has recently been proposed. Rat models of prenatal malnutrition have provided major support for this theory on the basis of tail-cuff measurements. However, this technique requires restraint and elevated temperature, both potential sources of stress. To determine the effect of prenatal protein malnutrition on blood pressure under nonstress conditions, 24-hour radiotelemetric measurements were taken in the home cage. Male rats born to dams fed a 6% casein diet for 5 weeks before mating and throughout pregnancy were studied in early adulthood (from 96 days of age). During the waking phase of their cycle but not the sleep phase, prenatal malnutrition gave rise to small but significant elevations of diastolic blood pressure and heart rate compared with well-nourished controls. Direct effects of stress on blood pressure responses were determined in a second experiment using an olfactory stressor. Prenatally malnourished rats showed a greater increase in both systolic and diastolic pressures compared with well-nourished controls during the first exposure to ammonia. A different pattern of change of cardiovascular responses was also observed during subsequent presentations of the stressor. These findings of a small baseline increase in diastolic pressure consequent to prenatal malnutrition, but an augmented elevation of both systolic and diastolic pressures after first exposure to stress, suggest the need to reevaluate interpretation of the large elevations in blood pressure previously observed in malnourished animals using the stressful tail-cuff procedure.
Hypertension 1998 Jul
PMID:Prenatal malnutrition-induced changes in blood pressure: dissociation of stress and nonstress responses using radiotelemetry. 967 46

Epidemiological evidence that hypertension and coronary heart disease are programmed by exposure to poor diet during intrauterine life, is supported by animal experiments. In the rat, fetal exposure to a maternal low protein diet is associated with abnormal fetal growth and later elevation of blood pressure. Fetal exposure to glucocorticoids of maternal origin are proposed to underlie this association. Pregnant female rats were fed control (18% casein) or moderately low protein diets (9% casein). Feeding of low protein was either throughout gestation (d0-22), or for specific periods (d0-7, d8-14, d15-22). Fetal and placental weight were determined at d14, 20 and 22. Low protein feeding in the periods d0-7, d8-14, d0-14 stimulated fetal growth to d14. At d20 gestation low protein exposed fetuses tended to be smaller than control fetuses, although low protein d8-14 fetuses were significantly larger than controls. Animals exposed to low protein diets were of lower weight at birth and had higher blood pressure at 4 weeks postnatal age. The activities of glucocorticoid-inducible enzymes in brain (fetal and neonatal) and liver (neonatal) were specifically elevated relative to control animals, by low protein exposure. The data suggest that low protein exposure, particularly in late gestation is associated with increased fetal glucocorticoid-exposure. This may both retard fetal growth and programme later increases in systolic blood pressure.
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PMID:Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets. 971 86

Epidemiological evidence suggests that hypertension and coronary heart disease are programmed by exposure to a poor diet during intrauterine life. It has been proposed that the prenatal environment may exert an adverse effect on the development of the kidney and hence later control of blood pressure. These assertions are supported by animal experiments. In the rat, fetal exposure to a maternal low protein diet is associated with disproportionate patterns of fetal growth and later elevation of blood pressure. Pregnant female rats were fed control (18% casein) or low protein diets throughout pregnancy, or during specific periods. Nephron number was determined at day 20 gestation, full term and 4 weeks of age. Exposure to low protein throughout gestation, or in mid-late gestation increased total nephron number at day 20. By term nephron number was reduced, relative to controls, in rats that were undernourished between days 8-14 or 15-22 gestation. At 4 weeks postnatally rats exposed to low protein throughout fetal life had a reduced (13%) nephron complement and blood pressures 13 mmHg above control animals. Lower renal size and elevated blood pressure persisted to 19 weeks of age, at which time glomerular filtration rate was normal. The data are consistent with the hypothesis that maternal undernutrition may programme the renal nephron number and hence impact upon adult blood pressure and the development of renal disease.
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PMID:Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. 1020 45

Prenatal exposure to maternal undernutrition in both humans and animals is associated with long-term changes in the structure, physiological functions and metabolism of key tissues and organs. This phenomenon, termed programming, is implicated in the aetiology of cardiovascular disease. Using an established rat model of hypertension programmed by prenatal protein restriction, assessment was made of the long-term influence of maternal diet upon prostaglandin metabolism. Pregnant rats were fed isoenergetic diets containing 18% casein (control) or 9% casein (low protein) from conception until littering. The offspring of these pregnancies were studied at day 20 of gestation, full-term gestation and at 4, 7 or 12 weeks postnatal age. Prostaglandin E(2) concentrations in plasma were similar in control and low-protein diet-exposed rats at 4 weeks of age. Urinary prostaglandin E(2) excretion was, however, significantly increased by prenatal undernutrition in rats at both 4 and 12 weeks postnatal age. The principal enzyme of prostaglandin E(2) degradation, 15-hydroxyprostaglandin dehydrogenase (PGDH) exhibited significantly lower activity in the kidneys of 4-week-old rats exposed to a maternal low-protein diet. This effect was transient and absent by 12 weeks postnatal age. There was also some evidence of an altered developmental profile of PGDH activity in the lungs of low-protein diet-exposed rats. These data are consistent with the long-term programming effects of the maternal diet upon renal prostaglandin metabolism. In the rat, increased local prostaglandin E(2) concentrations associated with impaired degradation may contribute to increased renovascular resistance and hypertension.
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PMID:Long-term modification of the excretion of prostaglandin E(2) by fetal exposure to a maternal low protein diet in the rat. 1043 8


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