Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat.
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.
Sherman
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RC
Institute of Human Nutrition, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Langley-Evans
S C
SC
D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018753:Diet, Protein-Restricted; D005260:Female; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D044140:Receptor, Angiotensin, Type 1; D009543:Nifedipine; D019808:Losartan