Skip to main content

Advertisement

Log in

Stunting growth: association of the blood pressure levels and ACE activity in early childhood

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and inactive bradykinin. Several studies carried out in our laboratory have consistently identified three isoforms of ACE, at 65, 90 and 190 kDa, with the 90-kDa isoform being a possible genetic marker of hypertension. Based on these observations and the fact that nutritional stunting can be associated with hypertension, we have investigated the expression and activity of ACE in stunted children and its association with blood pressure (BP) levels and nutritional state. Sixty children aged 2–7 years were selected for this study. A urine sample was collected from each child. Angiotensin converting enzyme activity was evaluated using two different substrates, and ACE expression was detected by Western blotting. Our results show that nutritional stunting is associated with high ACE activity in childhood and that adjustment by gender does not modify the strength of this association. A greater percentage of stunted children had increased BP levels, and this clinical parameter was inversely correlated with anthropometric indicators. A greater urinary protein expression of the three ACE isoforms was observed in the group of children with growth stunting. Our findings suggest that the reported high risk of hypertension in stunted adolescents and adults are, at least partly, associated with abnormalities in the renin–angiotensin system.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Sedgh G, Herrera GM, Nestel P, El Amin A, Fawzi WW (2000) Dietary vitamin A intake and nondietary factors are associated with reversal of stunting in children. J Nutr 130:2520–2526

    Article  CAS  Google Scholar 

  2. Allen LH, Gillespie SR (2001) Improving child growth: In: ACC/SCN (eds) What works? A review of the efficacy and effectiveness of nutrition interventions. United Nations Administrative Committee on Coordinator/Sub-Committee on Nutrition (ACC/SCN) in collaboration with the Asian Development Bank. United Nations University Press, Manila/Geneva, pp 23–41

  3. Moore SE, Halsall I, Howarth D, Poskitt EM, Prentice AM (2001) Glucose, insulin and lipid metabolism in rural Gambians exposed to early malnutrition. Diabet Med 18:646–653

    Article  CAS  Google Scholar 

  4. Gonzalez-Barranco J, Rios-Torres JM, Castillo-Martinez L, Lopez-Alvarenga JC, Aguilar-Salinas CA, Bouchard C, Depre’s JP, Tremblay A (2003) Effect of malnutrition during the first year of life on adult plasma insulin and glucose tolerance. Metabolism 52:1005–1011

    Article  CAS  Google Scholar 

  5. Sawaya AL, Grillo LP, Verreschi I, Carlos da Silva A, Roberts SB (1997) Mild stunting is associated with higher susceptibility to the effects of high-fat diets: studies in a shantytown population in São Paulo, Brazil. J Nutr 128:415S–420S

    Article  Google Scholar 

  6. Martins PA, Sawaya AL (2006) Evidence for impaired insulin production and higher sensitivity in stunted children living in slums. Br J Nutr 95:996–1001

    Article  CAS  Google Scholar 

  7. Sesso R, Barreto GP, Neves J, Sawaya AL (2004) Malnutrition is associated with increased blood pressure in childhood. Nephron Clin Pract 97:61–66

    Article  Google Scholar 

  8. Fernandes MT, Sesso R, Martins PA, Sawaya AL (2003) Increased blood pressure in adolescents of low socioeconomic status with short stature. Pediatr Nephrol 18:435–439

    PubMed  Google Scholar 

  9. Florêncio TT, Ferreira HS, Cavalcante JC, Sawaya AL (2004) Short stature, obesity and arterial hypertension in a very low income population in North-Eastern Brazil. Nutr Metab Cardiovasc Dis 14:26–33

    Article  Google Scholar 

  10. Erdos EG (1976) Conversion of angiotensin I to angiotensin II. Am J Med 60:749–759

    Article  CAS  Google Scholar 

  11. Hall JE (2003) Historical perspective of the renin-angiotensin system. Mol Biotechnol 24:27–39

    Article  CAS  Google Scholar 

  12. Henriksen EJ, Jacob S (2003) Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol 196:171–179

    Article  CAS  Google Scholar 

  13. Soubrier F, Alhenc-Gelas F, Hubert C (1988) Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci USA 85:9386–9390

    Article  CAS  Google Scholar 

  14. Casarini DE, Carmona AK, Plavnik FL, Zanella MT, Juliano L, Ribeiro AB (1995) Calcium channel blockers as inhibitors of angiotensin I-converting enzyme. Hypertension 26:1145–1148

    Article  CAS  Google Scholar 

  15. Casarini DE, Plavnik FL, Zanella MT, Marson O, Krieger JE, Hirata IY, Stella RC (2001) Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme. Int J Biochem Cell Biol 33:75–85

    Article  CAS  Google Scholar 

  16. Marques GD, Quinto BM, Plavnik FL, Krieger JE, Marson O, Casarini DE (2003) N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension. Hypertension 42:693–701

    Article  CAS  Google Scholar 

  17. Maluf LCV, Aragão DS, Mill JG, Sesso R, Casarini DE (2006) Populational study to determine the prevalence of the N-domain form of angiotensin of converting enzyme with 90 kDa described as a genetic marker of hypertension. J Hypertens 24:S183

    Google Scholar 

  18. Torun B, Chew F (1994) Protein-energy malnutrition. In: Shils ME, Olson JA, Shike M (eds) Modern nutrition in health and disease, vol 2, 8th edn. Lea and Febiger, Philadelphia, pp 950–976

    Google Scholar 

  19. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:1–22

    Article  Google Scholar 

  20. Friedland J, Silverstein E (1976) A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 66:416–424

    Article  CAS  Google Scholar 

  21. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  Google Scholar 

  22. Riviere G, Michaud A, Breton C, VanCamp G, Laborie C, Enache M, Lesage J, Deloof S, Corvol P, Vieau D (2005) Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat. Hypertension 46:1169–1174

    Article  CAS  Google Scholar 

  23. Ceravolo GS, Franco MC, Carneiro-Ramos MS, Carvalho MHC (2007) Enalapril and losartan restored blood pressure and vascular reactivity in intrauterine undernourished rats. Life Sci 80:782–787

    Article  CAS  Google Scholar 

  24. Cambien F, Leger J, Mallet C, Levy-Marchal C, Collin D, Czernichow P (1998) Angiotensin I-converting enzyme gene polymorphism modulates the consequences of in utero growth retardation on plasma insulin in young adults. Diabetes 47:470–475

    Article  CAS  Google Scholar 

  25. Franco MC, Higa EM, D’Almeida V, de Sousa FG, Sawaya AL, Fortes ZB, Sesso R (2007) Homocysteine and nitric oxide are related to blood pressure and vascular function in small-for-gestational-age children. Hypertension 50:396–402

    Article  CAS  Google Scholar 

  26. Barker DJ (1990) The fetal origins of type 2 diabetes mellitus. Ann Intern Med 130:322–324

    Article  Google Scholar 

  27. Schreuder M, Delemarre-van de Waal H, van Wijk A (2006) Consequences of intrauterine growth restriction for the kidney. Kidney Blood Press Res 29:108–125

    Article  CAS  Google Scholar 

  28. Lauer RM, Clarke WR (1989) Childhood risk factors for high adult blood pressure: The Muscatine study. Pediatrics 84:633–641

    CAS  PubMed  Google Scholar 

  29. Bao W, Threefoot AS, Srinivasan SR, Berenson GS (1995) Essential hypertension predicted by tracking of elevated blood pressure from childhood to adulthood: The Bogalusa Heart Study. Am J Hypertens 8:657–665

    Article  CAS  Google Scholar 

  30. Bastos HD, Macedo CS, Riyuzo MC (1993) Pressão arterial na infância. J Pediatr 69:107–115

    Google Scholar 

  31. Oliveira RG, Lamounier JA, Oliveira ADB, Castro MDR, Oliveira JS (1999) Blood pressure in school children and adolescents – The Belo Horizonte study. J Pediatr (Rio J) 75:256–266

    Article  CAS  Google Scholar 

  32. Langley-Evans SC (1997) Intrauterine programming of hypertension by glucocorticoids. Life Sci 60:1213–1221

    Article  CAS  Google Scholar 

  33. Langley-Evans SC, Sherman RC (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 (Colch) 94:373–381

    Article  Google Scholar 

  34. Salzer-Muhar U, Graninger W, Salzer HR, Wimmer M (1990) Angiotensin converting enzyme activity in children with congenital heart disease. Eur J Pediatr 150:19–21

    Article  CAS  Google Scholar 

  35. Franco MC, Casarini DE, Carneiro-Ramos MS, Sawaya AL, Barreto-Chaves ML, Sesso R (2007) Circulating renin angiotensin system and catecholamines in childhood: is there a role for birth weight? Clin Sci (Lond) 114:385–380

    Google Scholar 

  36. Serdaroglu E, Mir S, Berdeli A (2005) Hypertension and ACE gene insertion/deletion polymorphism in pediatric renal transplant patients. Pediatr Transplant 9:612–617

    Article  CAS  Google Scholar 

  37. Nordfeldt S, Samuelsson U (2003) Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes. Diabetes Care 26:274–278

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank the mothers and children who participated in this study. We are also grateful to the FAPESP and CNPq for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dulce Elena Casarini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Febba, A., Sesso, R., Barreto, G.P. et al. Stunting growth: association of the blood pressure levels and ACE activity in early childhood. Pediatr Nephrol 24, 379–386 (2009). https://doi.org/10.1007/s00467-008-0980-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-008-0980-1

Keywords

Navigation