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.
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Research Article|
February 09 2000
Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat
Rachel C. SHERMAN;
Rachel C. SHERMAN
*Institute of Human Nutrition, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
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Simon C. LANGLEY-EVANS
†University College Northampton, Boughton Green Road, Northampton NN2 7AL, U.K.
Correspondence: Dr. Simon Langley-Evans (e-mail simon.langley-evans@northampton.ac.uk).
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Publisher: Portland Press Ltd
Received:
September 03 1999
Revision Received:
October 05 1999
Accepted:
November 30 1999
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (3): 269–275.
Article history
Received:
September 03 1999
Revision Received:
October 05 1999
Accepted:
November 30 1999
Citation
Rachel C. SHERMAN, Simon C. LANGLEY-EVANS; Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clin Sci (Lond) 1 March 2000; 98 (3): 269–275. doi: https://doi.org/10.1042/cs0980269
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