Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-19T10:58:46.842Z Has data issue: false hasContentIssue false
  • English
  • Français

Long-term programming of blood pressure by maternal dietary iron restriction in the rat

Published online by Cambridge University Press:  09 March 2007

Rohan M. Lewis ,
Alison J. Forhead ,
Clive J. Petry ,
Susan E. Ozanne  and
C. Nicolas Hales
Rohan M. Lewis*
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, UK
Alison J. Forhead
Affiliation:
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Clive J. Petry
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, UK
Susan E. Ozanne
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, UK
C. Nicolas Hales
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QR, UK
*
*Corresponding author:Dr Rohan M. Lewis, present address, FOAD Research Division, University of Southampton, Level F, Princess Ann Hospital, Mail point 815, Coxford Road, Southampton SO17 5YA, UK, fax +44 23 8078 6933, email rml2@soton.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

We have reported that blood pressure was elevated in 3-month-old rats whose mothers were Fe-restricted during pregnancy. These animals also had improved glucose tolerance and decreased serum triacylglycerol. The aim of the present study was to determine whether these effects of maternal nutritional restriction, present in these animals at 3 months of age, can be observed in the same animals in later life. Pulmonary and serum angiotensin converting enzyme (ACE) concentrations were also measured to investigate whether the renin–angiotensin system was involved in the elevation of blood pressure observed in the offspring of Fe-restricted dams. Systolic blood pressure was higher in the offspring of Fe-restricted dams at 16 months of age. Heart and kidney weight were increased as a proportion of body weight in the offspring of Fe-restricted dams. The pulmonary ACE concentration was not significantly different between the groups. The serum ACE concentration was significantly elevated in the offspring of Fe-restricted dams at 3 but not 14 months of age. There was a strong correlation between serum ACE levels at 3 and 14 months of age. Glucose tolerance and serum insulin were not different between the maternal diet groups. Serum triacylglycerol tended to be lower in the offspring of Fe-restricted dams. There were no differences in serum non-esterified fatty acids or serum cholesterol between the maternal diet groups. This study provides further evidence that maternal nutrition has effects on the offspring that persist throughout life. At 16 months of age, the elevation of blood pressure in Fe-restricted offspring does not appear to be mediated via changes in ACE levels. Both cardiac hypertrophy and decreased serum triacylglycerol have also been observed in Fe-restricted fetuses, suggesting that these changes may be initiated in utero.

Keywords

Maternal iron deficiencyGrowth retardationBlood pressureTriacylglycerol
Type
Research Article
Information
British Journal of Nutrition , Volume 88 , Issue 3 , September 2002 , pp. 283 - 290
Copyright
Copyright © The Nutrition Society 2002

References

Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR & Edwards, CR (1993) Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 341, 339–341.CrossRefGoogle ScholarPubMed
Bertram, C, Trowern, AR, Copin, N, Jackson, AA & Whorwood, CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11 beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142, 2841–2853.CrossRefGoogle Scholar
Crowe, C, Dandekar, P, Fox, M, Dhingra, K, Bennet, L & Hanson, MA (1995) The effects of anaemia on heart, placenta and body weight, blood pressure in fetal and neonatal rats. Journal of Physiology 488, 515–519.CrossRefGoogle ScholarPubMed
Desai, M, Crowther, NJ, Lucas, A & Hales, CN (1996) Organ-selective growth in the offspring of protein-restricted mothers. British Journal of Nutrition 76, 591–603.CrossRefGoogle ScholarPubMed
Felt, BT & Lozoff, B (1996) Brain iron and behavior of rats are not normalized by treatment of iron deficiency anemia during early development. Journal of Nutrition 126, 693–701.CrossRefGoogle Scholar
Forhead, AJ, Gillespie, CE & Fowden, AL (2000) Role of cortisol in the ontogenic control of pulmonary and renal angiotensin-converting enzyme in fetal sheep near term. Journal of Physiology 526, 409–416.CrossRefGoogle ScholarPubMed
Gambling, L, Danzeisen, R, Gair, S, Lea, RG, Charania, Z, Solanky, N, Joory, KD, Srai, SK & McArdle, HJ (2001) Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochemical Journal 356, 883–889.CrossRefGoogle ScholarPubMed
Hales, CN, Desai, M, Ozanne, SE & Crowther, NJ (1996) Fishing in the stream of diabetes: from measuring insulin to the control. Biochemical Society Transactions 24, 341–350.CrossRefGoogle ScholarPubMed
Langley, SC, Browne, RF & Jackson, AA (1994) Altered glucose tolerance in rats exposed to maternal low protein diets in utero. Comparative Biochemistry and Physiology 109, 223–229.CrossRefGoogle ScholarPubMed
Langley, SC & Jackson, AA (1994) Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clinical Science 86, 217–222.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1997) Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. Clinical Science 93, 423–429.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Jackson, AA (1995) Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comparative Biochemistry and Physiology 110, A223–A228.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Sherman, RC, Welham, SJ, Nwagwu, MO, Gardner, DS & Jackson, AA (1999 a) Intrauterine programming of hypertension: the role of the renin–angiotensin system. Biochemical Society Transactions 27, 88–93.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJ & Jackson, AA (1999 b) Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Science 64, 965–974.CrossRefGoogle ScholarPubMed
Law, CM & Shiell, AW (1996) Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. Journal of Hypertension 14, 935–941.CrossRefGoogle ScholarPubMed
Lewis, RM, James, LA, Zhang, J, Byrne, CD & Hales, CN (2001 a) Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels. British Journal of Nutrition 85, 193–201.CrossRefGoogle ScholarPubMed
Lewis, RM, Petry, CJ, Ozanne, SE & Hales, CN (2001 b) Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, serum lipids in the 3-month-old offspring. Metabolism 50, 562–567.CrossRefGoogle ScholarPubMed
Lindsay, RM, Edwards, CR & Seckl, JR (1996) Inhibition of 11-beta-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring. Hypertension 27, 1200–1204.CrossRefGoogle ScholarPubMed
Lowry, OH, Rosenbrough, NJ, Farr, AL & Randall, RJ (1951) Protein measurement with Folin–phenol reagent. Journal of Biological Chemistry 193, 267–275.CrossRefGoogle ScholarPubMed
Lucas, A, Baker, BA, Desai, M & Hales, CN (1996) Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. British Journal of Nutrition 76, 605–612.CrossRefGoogle ScholarPubMed
Marchand, MC & Langley-Evans, SC (2001) Intrauterine programming of nephron number: the fetal flaw revisited. Journal of Nephrology 14, 327–331.Google ScholarPubMed
Petry, CJ, Dorling, MW, Palwak, DB, Ozanne, SE & Hales, CN (2001) Diabetes in old male offspring of rat dams fed a reduced protein diet. International Journal of Experimental Diabetes Research 2, 139–143.CrossRefGoogle ScholarPubMed
Rigat, B, Hubert, C, Alhenc-Gelas, F, Cambien, F, Corvol, P & Soubrier, F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. Journal of Clinical Investigation 86, 1343–1346.CrossRefGoogle ScholarPubMed
Santhamma, KR & Sen, I (2000) Specific cellular proteins associate with angiotensin-converting enzyme and regulate its intracellular transport and cleavage-secretion. Journal of Biological Chemistry 275, 23253–23258.CrossRefGoogle ScholarPubMed
Shepherd, PR, Crowther, NJ, Desai, M, Hales, CN & Ozanne, SE (1997) Altered adipocyte properties in the offspring of protein malnourished rats. British Journal of Nutrition 78, 121–129.CrossRefGoogle ScholarPubMed
Sherman, AR & Moran, PE (1984) Copper metabolism in iron-deficient maternal and neonatal rats. Journal of Nutrition 114, 298–306.CrossRefGoogle ScholarPubMed
Sherman, RC & Langley-Evans, SC (1998) 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. Clinical Science 94, 373–381.CrossRefGoogle ScholarPubMed
Sherman, RC & Langley-Evans, SC (2000) Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clinical Science 98, 269–275.CrossRefGoogle ScholarPubMed
Vehaskari, VM, Aviles, DH & Manning, J (2001) Prenatal programming of adult hypertension in the rat. Kidney International 59, 238–245.CrossRefGoogle ScholarPubMed
Woodall, SM, Johnston, BM, Breier, BH & Gluckman, PD (1996) Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatric Research 40, 438–443.CrossRefGoogle ScholarPubMed