Skip to main content
SpringerLink
Log in

Programming of Essential Hypertension: What Pediatric Cardiologists Need to Know

  • Review Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Hypertension is recognized as one of the major contributing factors to cardiovascular disease, but its etiology remains incompletely understood. Known genetic and environmental influences can only explain a small part of the variability in cardiovascular disease risk. The missing heritability is currently one of the most important challenges in blood pressure and hypertension genetics. Recently, some promising approaches have emerged that move beyond the DNA sequence and focus on identification of blood pressure genes regulated by epigenetic mechanisms such as DNA methylation, histone modification and microRNAs. This review summarizes information on gene–environmental interactions that lead toward the developmental programming of hypertension with specific reference to epigenetics and provides pediatricians and pediatric cardiologists with a more complete understanding of its pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. A global brief on hypertension (2013) http://apps.who.int/iris/bitstream/10665/79059/1/WHO_DCO_WHD_2013.2_eng.pdf

  2. Baccarelli A, Ghosh S (2012) Environmental exposures, epigenetics and cardiovascular disease. Curr Opin Clin Nutr Metab Care 15(4):323–329

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME (1989) Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298(6673):564–567

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Barker DJ, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS (1993) Fetal nutrition and cardiovascular disease in adult life. Lancet 341(8850):938–941

    Article  CAS  PubMed  Google Scholar 

  5. Baum M (2010) Role of the kidney in the prenatal and early postnatal programming of hypertension. Am J Physiol Renal Physiol 298(2):F235–F247

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR (1993) Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 341(8841):339–341

    Article  CAS  PubMed  Google Scholar 

  7. Bertram CE, Hanson MA (2001) Animal models and programming of the metabolic syndrome. Br Med Bull 60:103–121

    Article  CAS  PubMed  Google Scholar 

  8. Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ (2007) Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res 100(4):520–526

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Bogdarina I, Haase A, Langley-Evans S, Clark AJ (2010) Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat. PLoS ONE 5(2):e9237

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Braun MC, Doris PA (2012) Mendelian and trans-generational inheritance in hypertensive renal disease. Ann Med 44(Suppl 1):S65–S73

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Bruce KD, Hanson MA (2010) The developmental origins, mechanisms, and implications of metabolic syndrome. J Nutr 140(3):648–652

    Article  CAS  PubMed  Google Scholar 

  12. Campbell AL, Murphy BE (1977) The maternal-fetal cortisol gradient during pregnancy and at delivery. J Clin Endocrinol Metab 45(3):435–440

    Article  CAS  PubMed  Google Scholar 

  13. Campbell DM, Hall MH, Barker DJ, Cross J, Shiell AW, Godfrey KM (1996) Diet in pregnancy and the offspring’s blood pressure 40 years later. Br J Obstet Gynaecol 103(3):273–280

    Article  CAS  PubMed  Google Scholar 

  14. Cattanach BM, Beechey CV (1990) Autosomal and X-chromosome imprinting. Development 108(Suppl):63–72

    Google Scholar 

  15. Causes of death (2008) Data sources and methods 2011. http://www.who.int/healthinfo/global_burden_disease/cod_2008_sources_methods.pdf

  16. Cole TJ, Blendy JA, Monaghan AP, Schmid W, Aguzzi A, Schutz G (1995) Molecular genetic analysis of glucocorticoid signaling during mouse development. Steroids 60(1):93–96

    Article  CAS  PubMed  Google Scholar 

  17. Cottrell EC, Seckl JR (2009) Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 3:19

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Crider KS, Yang TP, Berry RJ, Bailey LB (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr 3(1):21–38

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Curhan GC, Chertow GM, Willett WC, Spiegelman D, Colditz GA, Manson JE et al (1996) Birth weight and adult hypertension and obesity in women. Circulation 94(6):1310–1315

    Article  CAS  PubMed  Google Scholar 

  20. Dagan A, Kwon HM, Dwarakanath V, Baum M (2008) Effect of renal denervation on prenatal programming of hypertension and renal tubular transporter abundance. Am J Physiol Renal Physiol 295(1):F29–F34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Ding Y, Lv J, Mao C, Zhang H, Wang A, Zhu L et al (2010) High-salt diet during pregnancy and angiotensin-related cardiac changes. J Hypertens 28(6):1290–1297

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Dodic M, Abouantoun T, O’Connor A, Wintour EM, Moritz KM (2002) Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension 40(5):729–734

    Article  CAS  PubMed  Google Scholar 

  23. Dodic M, McAlinden AT, Jefferies AJ, Wintour EM, Cock ML, May CN et al (2006) Differential effects of prenatal exposure to dexamethasone or cortisol on circulatory control mechanisms mediated by angiotensin II in the central nervous system of adult sheep. J Physiol 571(Pt 3):651–660

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Doris PA (2002) Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension 39(2 Pt 2):323–331

    Article  CAS  PubMed  Google Scholar 

  25. Drake AJ, Tang JI, Nyirenda MJ (2007) Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease. Clin Sci 113(5):219–232

    Article  CAS  PubMed  Google Scholar 

  26. Edwards LJ, McMillen IC (2002) Periconceptional nutrition programs development of the cardiovascular system in the fetal sheep. Am J Physiol Regul Integr Comp Physiol 283(3):R669–R679

    Article  CAS  PubMed  Google Scholar 

  27. Erhuma A, McMullen S, Langley-Evans SC, Bennett AJ (2009) Feeding pregnant rats a low-protein diet alters the hepatic expression of SREBP-1c in their offspring via a glucocorticoid-related mechanism. Endocrine 36(2):333–338

    Article  CAS  PubMed  Google Scholar 

  28. Filler G, Yasin A, Kesarwani P, Garg AX, Lindsay R, Sharma AP (2011) Big mother or small baby: which predicts hypertension? J Clin Hypertens 13(1):35–41

    Article  Google Scholar 

  29. Forrester TE, Wilks RJ, Bennett FI, Simeon D, Osmond C, Allen M et al (1996) Fetal growth and cardiovascular risk factors in Jamaican schoolchildren. BMJ 312(7024):156–160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Franco MC, Christofalo DM, Sawaya AL, Ajzen SA, Sesso R (2006) Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels. Hypertension 48(1):45–50

    Article  CAS  PubMed  Google Scholar 

  31. Franco MC, Casarini DE, Carneiro-Ramos MS, Sawaya AL, Barreto-Chaves ML, Sesso R (2008) Circulating renin-angiotensin system and catecholamines in childhood: is there a role for birthweight? Clin Sci 114(5):375–380

    Article  CAS  PubMed  Google Scholar 

  32. Gambling L, Dunford S, Wallace DI, Zuur G, Solanky N, Srai SK et al (2003) Iron deficiency during pregnancy affects postnatal blood pressure in the rat. J Physiol 552(Pt 2):603–610

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Gardner DS, Pearce S, Dandrea J, Walker R, Ramsay MM, Stephenson T et al (2004) Peri-implantation undernutrition programs blunted angiotensin II evoked baroreflex responses in young adult sheep. Hypertension 43(6):1290–1296

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Ghildiyal M, Zamore PD (2009) Small silencing RNAs: an expanding universe. Nat Rev Genet 10(2):94–108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Ghoshal K, Li X, Datta J, Bai S, Pogribny I, Pogribny M et al (2006) A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats. J Nutr 136(6):1522–1527

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Global status report on noncommunicable diseases (2010) Geneva: World Health Organization, 2011

  37. Gluckman PD, Hanson MA (2004) Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 56(3):311–317

    Article  PubMed  Google Scholar 

  38. Gluckman PD, Hanson MA, Buklijas T, Low FM, Beedle AS (2009) Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol 5(7):401–408

    Article  CAS  PubMed  Google Scholar 

  39. Godfrey KM (2002) The role of the placenta in fetal programming-a review. Placenta 23(Suppl A):S20–S27

    Article  PubMed  Google Scholar 

  40. Godfrey KM, Forrester T, Barker DJ, Jackson AA, Landman JP, Hall JS et al (1994) Maternal nutritional status in pregnancy and blood pressure in childhood. Br J Obstet Gynaecol 101(5):398–403

    Article  CAS  PubMed  Google Scholar 

  41. Gopalakrishnan GS, Gardner DS, Rhind SM, Rae MT, Kyle CE, Brooks AN et al (2004) Programming of adult cardiovascular function after early maternal undernutrition in sheep. Am J Physiol Regul Integr Comp Physiol 287(1):R12–R20

    Article  CAS  PubMed  Google Scholar 

  42. Guarnieri DJ, DiLeone RJ (2008) MicroRNAs: a new class of gene regulators. Ann Med 40(3):197–208

    Article  CAS  PubMed  Google Scholar 

  43. Guerrero-Bosagna C, Skinner MK (2012) Environmentally induced epigenetic transgenerational inheritance of phenotype and disease. Mol Cell Endocrinol 354(1–2):3–8

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Hadoke PW, Lindsay RS, Seckl JR, Walker BR, Kenyon CJ (2006) Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure. J Endocrinol 188(3):435–442

    Article  CAS  PubMed  Google Scholar 

  45. Harrap SB, Van der Merwe WM, Griffin SA, Macpherson F, Lever AF (1990) Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension 16(6):603–614

    Article  CAS  PubMed  Google Scholar 

  46. http://omim.org/entry/145500

  47. Huxley R, Neil A, Collins R (2002) Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Lancet 360(9334):659–665

    Article  PubMed  Google Scholar 

  48. Inagami T (1994) The renin-angiotensin system. Essays Biochem 28:147–164

    CAS  PubMed  Google Scholar 

  49. International Consortium for Blood Pressure Genome-Wide Association S, Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD et al (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478(7367):103–109

    Article  CAS  Google Scholar 

  50. Iwanami J, Mogi M, Iwai M, Horiuchi M (2009) Inhibition of the renin-angiotensin system and target organ protection. Hypertens Res 32(4):229–237

    Article  CAS  PubMed  Google Scholar 

  51. Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC (2002) Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clin Sci 103(6):633–639

    Article  CAS  PubMed  Google Scholar 

  52. Kerkel K, Spadola A, Yuan E, Kosek J, Jiang L, Hod E et al (2008) Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet 40(7):904–908

    Article  CAS  PubMed  Google Scholar 

  53. Khan IY, Taylor PD, Dekou V, Seed PT, Lakasing L, Graham D et al (2003) Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 41(1):168–175

    Article  CAS  PubMed  Google Scholar 

  54. Kind KL, Simonetta G, Clifton PM, Robinson JS, Owens JA (2002) Effect of maternal feed restriction on blood pressure in the adult guinea pig. Exp Physiol 87(4):469–477

    Article  PubMed  Google Scholar 

  55. King JC (2006) Maternal obesity, metabolism, and pregnancy outcomes. Ann Rev Nutr 26:271–291

    Article  CAS  Google Scholar 

  56. Kunes J, Kadlecova M, Vaneckova I, Zicha J (2012) Critical developmental periods in the pathogenesis of hypertension. Physiol Res 61(Suppl 1):S9–S17

    CAS  PubMed  Google Scholar 

  57. Kwong WY, Wild AE, Roberts P, Willis AC, Fleming TP (2000) Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127(19):4195–4202

    CAS  PubMed  Google Scholar 

  58. Langley-Evans SC (1997) Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. J Hypertens 15(5):537–544

    Article  CAS  PubMed  Google Scholar 

  59. Langley-Evans SC (2000) Critical differences between two low protein diet protocols in the programming of hypertension in the rat. Int J Food Sci Nutr 51(1):11–17

    Article  CAS  PubMed  Google Scholar 

  60. Langley-Evans SC (2006) Developmental programming of health and disease. Proc Nutr Soc 65(1):97–105

    Article  PubMed Central  PubMed  Google Scholar 

  61. Langley-Evans SC, Gardner DS, Jackson AA (1996) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fertil 106(2):307–312

    Article  CAS  PubMed  Google Scholar 

  62. Langley-Evans SC, Phillips GJ, Benediktsson R, Gardner DS, Edwards CR, Jackson AA et al (1996) Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta 17(2–3):169–172

    Article  CAS  PubMed  Google Scholar 

  63. Leon DA, Lithell HO, Vagero D, Koupilova I, Mohsen R, Berglund L et al (1998) Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915–29. BMJ 317(7153):241–245

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A et al (2009) Genome-wide association study of blood pressure and hypertension. Nat Genet 41(6):677–687

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Lillycrop KA (2011) Effect of maternal diet on the epigenome: implications for human metabolic disease. Proc Nutr Soc 70(1):64–72

    Article  PubMed  Google Scholar 

  66. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135(6):1382–1386

    CAS  PubMed  Google Scholar 

  67. Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC (2007) Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr 97(6):1064–1073

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H et al (2012) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380(9859):2224–2260

    Article  PubMed Central  PubMed  Google Scholar 

  69. Loos RJ, Fagard R, Beunen G, Derom C, Vlietinck R (2001) Birth weight and blood pressure in young adults: a prospective twin study. Circulation 104(14):1633–1638

    Article  CAS  PubMed  Google Scholar 

  70. Lucas A, Morley R (1994) Does early nutrition in infants born before term programme later blood pressure? BMJ 309(6950):304–308

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Luyckx VA, Brenner BM (2005) Low birth weight, nephron number, and kidney disease. Kidney Int Suppl 97:S68–S77

    Article  PubMed  Google Scholar 

  72. Ma RC, Chan JC, Tam WH, Hanson MA, Gluckman PD (2013) Gestational diabetes, maternal obesity, and the NCD burden. Clin Obstet Gynecol 56(3):633–641

    Article  PubMed  Google Scholar 

  73. Manalich R, Reyes L, Herrera M, Melendi C, Fundora I (2000) Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58(2):770–773

    Article  CAS  PubMed  Google Scholar 

  74. May R (2007) Prepregnancy weight, inappropriate gestational weight gain, and smoking: relationships to birth weight. Am J Hum Biol 19(3):305–310

    Article  PubMed  Google Scholar 

  75. Moritz KM, Singh RR, Probyn ME, Denton KM (2009) Developmental programming of a reduced nephron endowment: more than just a baby’s birth weight. Am J Physiol Renal Physiol 296(1):F1–F9

    Article  CAS  PubMed  Google Scholar 

  76. Naimi TS, Lipscomb LE, Brewer RD, Gilbert BC (2003) Binge drinking in the preconception period and the risk of unintended pregnancy: implications for women and their children. Pediatrics 111(5 Pt 2):1136–1141

    PubMed  Google Scholar 

  77. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L et al (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet 41(6):666–676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Nuyt AM (2008) Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models. Clin Sci 114(1):1–17

    Article  CAS  PubMed  Google Scholar 

  79. Nwagwu MO, Cook A, Langley-Evans SC (2000) Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero. Br J Nutr 83(1):79–85

    CAS  PubMed  Google Scholar 

  80. O’Regan D, Kenyon CJ, Seckl JR, Holmes MC (2004) Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology. Am J Physiol Endocrinol Metab 287(5):E863–E870

    Article  PubMed  CAS  Google Scholar 

  81. Ortiz LA, Quan A, Zarzar F, Weinberg A, Baum M (2003) Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension 41(2):328–334

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Padmanabhan S, Melander O, Johnson T, Di Blasio AM, Lee WK, Gentilini D et al (2010) Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet 6(10):e1001177

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  83. Painter RC, Roseboom TJ, Bleker OP (2005) Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol 20(3):345–352

    Article  CAS  PubMed  Google Scholar 

  84. Pogribny IP, Karpf AR, James SR, Melnyk S, Han T, Tryndyak VP (2008) Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet. Brain Res 1237:25–34

    Article  CAS  PubMed  Google Scholar 

  85. Quinkler M, Stewart PM (2003) Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab 88(6):2384–2392

    Article  CAS  PubMed  Google Scholar 

  86. Radford EJ, Ferron SR, Ferguson-Smith AC (2011) Genomic imprinting as an adaptative model of developmental plasticity. FEBS Lett 585(13):2059–2066

    Article  CAS  PubMed  Google Scholar 

  87. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293(5532):1089–1093

    Article  CAS  PubMed  Google Scholar 

  88. Ritz E, Amann K, Koleganova N, Benz K (2011) Prenatal programming-effects on blood pressure and renal function. Nat Rev Nephrol 7(3):137–144

    Article  PubMed  Google Scholar 

  89. Roseboom TJ, van der Meulen JH, Ravelli AC, van Montfrans GA, Osmond C, Barker DJ et al (1999) Blood pressure in adults after prenatal exposure to famine. J Hypertens 17(3):325–330

    Article  CAS  PubMed  Google Scholar 

  90. Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2001) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Res Off J Int Soc Twin Stud 4(5):293–298

    Article  CAS  Google Scholar 

  91. Seckl JR (1997) Glucocorticoids, feto-placental 11 beta-hydroxysteroid dehydrogenase type 2, and the early life origins of adult disease. Steroids 62(1):89–94

    Article  CAS  PubMed  Google Scholar 

  92. Sharma S, Ding F, Dokholyan NV (2007) Multiscale modeling of nucleosome dynamics. Biophys J 92(5):1457–1470

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. 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. Clin Sci 94(4):373–381

    Article  CAS  PubMed  Google Scholar 

  94. Sherman RC, Langley-Evans SC (2000) Antihypertensive treatment in early postnatal life modulates prenatal dietary influences upon blood pressure in the rat. Clin Sci 98(3):269–275

    Article  CAS  PubMed  Google Scholar 

  95. Sinclair KD, Allegrucci C, Singh R, Gardner DS, Sebastian S, Bispham J et al (2007) DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci USA 104(49):19351–19356

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Singh RR, Cullen-McEwen LA, Kett MM, Boon WM, Dowling J, Bertram JF et al (2007) Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring. J Physiol 579(Pt 2):503–513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Singhal A, Cole TJ, Lucas A (2001) Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet 357(9254):413–419

    Article  CAS  PubMed  Google Scholar 

  98. Singhal A, Cole TJ, Fewtrell M, Kennedy K, Stephenson T, Elias-Jones A et al (2007) Promotion of faster weight gain in infants born small for gestational age: is there an adverse effect on later blood pressure? Circulation 115(2):213–220

    Article  PubMed  Google Scholar 

  99. Snieder H, Harshfield GA, Treiber FA (2003) Heritability of blood pressure and hemodynamics in African- and European-American youth. Hypertension 41(6):1196–1201

    Article  CAS  PubMed  Google Scholar 

  100. Spencer J, Wang Z, Hoy W (2001) Low birth weight and reduced renal volume in Aboriginal children. Am J Kidney Dis 37(5):915–920

    Article  CAS  PubMed  Google Scholar 

  101. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ (1996) Fetal growth and coronary heart disease in south India. Lancet 348(9037):1269–1273

    Article  CAS  PubMed  Google Scholar 

  102. Stelloh C, Allen KP, Mattson DL, Lerch-Gaggl A, Reddy S, El-Meanawy A (2012) Prematurity in mice leads to reduction in nephron number, hypertension, and proteinuria. Transl Res 159(2):80–89

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Sun K, Yang K, Challis JR (1997) Differential expression of 11 beta-hydroxysteroid dehydrogenase types 1 and 2 in human placenta and fetal membranes. J Clin Endocrinol Metab 82(1):300–305

    CAS  PubMed  Google Scholar 

  104. Surani MA (2001) Reprogramming of genome function through epigenetic inheritance. Nature 414(6859):122–128

    Article  CAS  PubMed  Google Scholar 

  105. Symonds ME, Stephenson T, Budge H (2009) Early determinants of cardiovascular disease: the role of early diet in later blood pressure control. Am J Clin Nutr 89(5):1518S–1522S

    Article  CAS  PubMed  Google Scholar 

  106. Timberlake DS, O’Connor DT, Parmer RJ (2001) Molecular genetics of essential hypertension: recent results and emerging strategies. Curr Opin Nephrol Hypertens 10(1):71–79

    Article  CAS  PubMed  Google Scholar 

  107. Tomaszewski M, Debiec R, Braund PS, Nelson CP, Hardwick R, Christofidou P et al (2010) Genetic architecture of ambulatory blood pressure in the general population: insights from cardiovascular gene-centric array. Hypertension 56(6):1069–1076

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  108. Udali S, Guarini P, Moruzzi S, Choi SW, Friso S (2013) Cardiovascular epigenetics: from DNA methylation to microRNAs. Mol Aspects Med 34(4):883–901

    Article  CAS  PubMed  Google Scholar 

  109. Wang X, Snieder H (2010) Genome-wide association studies and beyond: what’s next in blood pressure genetics? Hypertension 56(6):1035–1037

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Wang X, Prins BP, Sober S, Laan M, Snieder H (2011) Beyond genome-wide association studies: new strategies for identifying genetic determinants of hypertension. Curr Hypertens Rep 13(6):442–451

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Watkins AJ, Wilkins A, Cunningham C, Perry VH, Seet MJ, Osmond C et al (2008) Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J Physiol 586(8):2231–2244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. Watkins AJ, Lucas ES, Torrens C, Cleal JK, Green L, Osmond C et al (2010) Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring. Br J Nutr 103(12):1762–1770

    Article  CAS  PubMed  Google Scholar 

  113. Wesseling S, Koeners MP, Joles JA (2011) Salt sensitivity of blood pressure: developmental and sex-related effects. Am J Clin Nutr 94(6 Suppl):1928S–1932S

    Article  CAS  PubMed  Google Scholar 

  114. Wintour EM, Johnson K, Koukoulas I, Moritz K, Tersteeg M, Dodic M (2003) Programming the cardiovascular system, kidney and the brain: a review. Placenta 24(Suppl A):S65–S71

    Article  PubMed  CAS  Google Scholar 

  115. 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. Pediatr Res 40(3):438–443

    Article  CAS  PubMed  Google Scholar 

  116. Woods LL, Weeks DA, Rasch R (2004) Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int 65(4):1339–1348

    Article  PubMed  Google Scholar 

  117. Wu JN, Berecek KH (1993) Prevention of genetic hypertension by early treatment of spontaneously hypertensive rats with the angiotensin converting enzyme inhibitor captopril. Hypertension 22(2):139–146

    Article  CAS  PubMed  Google Scholar 

  118. Zandi-Nejad K, Luyckx VA, Brenner BM (2006) Adult hypertension and kidney disease: the role of fetal programming. Hypertension 47(3):502–508

    Article  CAS  PubMed  Google Scholar 

  119. Zicha J, Vaneckova I, Kunes J (2010) Systems analysis in hypertension: complementary role of physiologists and geneticists. Physiol Res 59(6):837–839

    CAS  PubMed  Google Scholar 

  120. Zimmermann H, Gardner DS, Jellyman JK, Fowden AL, Giussani DA, Forhead AJ (2003) Effect of dexamethasone on pulmonary and renal angiotensin-converting enzyme concentration in fetal sheep during late gestation. Am J Obstet Gynecol 189(5):1467–1471

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Pediatrics Department, Hospital do Espírito Santo de Évora, Largo Senhor da Pobreza, 7000-811, Évora, Portugal

    Joana Morgado

  2. Pediatrics Department, Hospital Garcia de Orta, Almada, Portugal

    Bruno Sanches

  3. Pediatric Cardiology Department, Hospital Santa Cruz, Lisbon, Portugal

    Rui Anjos

  4. Genetics Laboratory, Environmental Health Institute, Lisbon Medical School, Lisbon, Portugal

    Constança Coelho

Authors
  1. Joana Morgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruno Sanches
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Anjos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Constança Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joana Morgado.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morgado, J., Sanches, B., Anjos, R. et al. Programming of Essential Hypertension: What Pediatric Cardiologists Need to Know. Pediatr Cardiol 36, 1327–1337 (2015). https://doi.org/10.1007/s00246-015-1204-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-015-1204-7

Keywords

Search

Navigation