Prenatal Undernutrition Alters Postnatal Vascular Sensitivity to Angiotensin II

Gardner, David; Jackson, AA; Langley-Evans, SC

doi:10.1042/cs094002pc

Cited by 7 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The model used in the present study has yielded highly consistent effects of a maternal low-protein diet in rat pregnancy upon the blood pressure of the resulting offspring [8][9][10][11][12][13][14]17,18,26,27]. In keeping with the finding that individuals in the human population who are of low birthweight have increased blood pressure, rats exposed to low-protein diets in utero are of low to normal weight at birth and have blood pressures significantly above those of control animals.…”

Section: Discussionsupporting

confidence: 73%

“…Local renin-angiotensin systems in brain, heart and kidney may have a critical role in determining blood pressure. Preliminary data from cannulated, anaesthetized rats suggests that animals exposed to low-protein diets in utero are more sensitive to lower concentrations of infused angiotensin II [27], although it is unclear which target tissues mediate angiotensin-induced increases in resistance.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat

SHERMAN¹,

LANGLEY-EVANS²

2000

Clinical Science

View full text Add to dashboard Cite

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 AT(1) receptor between 2 and 4 weeks of age may be critically up-regulated by fetal factors, including exposure to glucocorticoids of maternal origin.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat

SHERMAN¹,

LANGLEY-EVANS²

2000

Clinical Science

View full text Add to dashboard Cite

show abstract

“…This may indicate a more rapid turnover of the peptide in plasma, possibly by virtue of increased receptor densities. This assertion is supported by the observation that the pressor response of low-proteinexposed rats to intravenously administered angiotensin I1 is greater than in control animals at low doses of the peptide [21].…”

Section: Discussionmentioning

confidence: 52%

“…This finding is similar to our previous reports which indicate that blood pressure rises in utero or during the suckling period and remains elevated to a similar extent throughout adult life, with no evidence of amplification. These observations using tail-cuff methodology have been verified directly in anaesthetized rats [21].…”

Section: Discussionmentioning

confidence: 96%

“…The degree of blood pressure elevation associated with intrauterine undernutrition measured in naive animals (24mmHg), was similar to that determined after 6 days of training (22 mmHg). Differences in blood pressures between rats exposed to low protein and control diets, as determined using the tail cuff, have been verified by direct methodology under anaesthesia [21].…”

Section: Blood Pressure Determinationmentioning

confidence: 99%

See 1 more Smart Citation

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

1998

View full text Add to dashboard Cite

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.

show abstract

Intrauterine programming of hypertension: the role of the renin-angiotensin system

Langley‐Evans¹,

Sherman

Welham

et al. 1999

Biochemical Society Transactions

121

View full text Add to dashboard Cite

From experiments with prenatal undernutrition in the rat, it is clear that fetal exposure to glucocorticoids of maternal origin is a key first step in the programming of hypertension and perhaps coronary heart disease. The chain of events leading from glucocorticoid action in the fetal tissues to hypertension in adulthood involves the development of hypersensitivity to glucocorticoids in adult life (Scheme 1). This has the effect of activating the RAS through induction of key genes such as ACE, which, in turn, may increase sensitivity of the blood vessels to the actions of ANGII. Another consequence of prenatal undernutrition, which may or may not involve glucocorticoids, is the abnormal development of the kidney [35]. Impaired nephrogenesis must surely have an impact upon lifelong renal function and cardiovascular control. Progress has been made in demonstrating that hypertension can be prenatally programmed through maternal dietary manipulation and some of the putative mechanisms involved have been identified. The priorities in this field of research must now be to clarify the role of maternal diet as a programming stimulus in order to generate an effective series of public health guidelines for pregnant women. Although the identification of metabolic mechanisms might suggest possible pharmacological interventions in early life as a means of reducing cardiovascular risk in adult life [49], it will always be more desirable to optimize maternal diet.

show abstract

Prenatal Undernutrition Alters Postnatal Vascular Sensitivity to Angiotensin II

Cited by 7 publications

References 0 publications

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat

Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat

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

Intrauterine programming of hypertension: the role of the renin-angiotensin system

Contact Info

Product

Resources

About