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Mechanisms of Disease: in utero programming in the pathogenesis of hypertension

Nature Clinical Practice Nephrology volume 2, pages 700–707 (2006)Cite this article

Abstract

Nutritional and other environmental cues during development can permanently alter the structure, homeostatic systems, and functions of the body. This phenomenon has been referred to as 'programming'. Epidemiological and animal studies show that programmed effects operate within the normal range of growth and development, and influence the risk of chronic disease in adult life. We review the evidence that these effects include reduced nephron number and compensatory adaptations, which might lead to hypertension, and perhaps accelerate the decline in renal function that accompanies aging. These processes might be exacerbated by programmed changes in vascular structure and function, and alterations in endocrine and metabolic homeostasis. Programmed effects might be initiated as early as the periconceptual phase of development, and could involve epigenetic changes in gene expression or altered stem cell allocation. Better understanding of these processes could lead to the development of novel diagnostic and preventive measures, and to early detection of at-risk individuals. By monitoring blood pressure, weight, and renal function in children, it might be possible to reduce the risk of cardiovascular and renal disease in later life.

Key Points

  • According to the 'fetal origins hypothesis', different forms of cardiovascular disease and type 2 diabetes originate from 'developmental plasticity', in response to undernutrition during fetal life and infancy

  • Mechanisms through which the path of development initiates hypertension include allocation of stem cells and alteration of gene expression in the embryo; changes in renal growth; and alterations in homeostatic set-points that control blood pressure

  • These changes can make affected systems more vulnerable to disruptive influences in postnatal life including obesity, environmental stress, oxidative stress, and high salt intake

  • By monitoring blood pressure, weight, diet, and renal function in children, it might be possible to reduce the risk of cardiovascular and renal disease in later life

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Figure 1: Growth of 1,404 boys and girls who later developed hypertension in a cohort of 8,760 children born in Helsinki, Finland.

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Acknowledgements

DJP Barker and MA Hanson received support from the British Heart Foundation. SP Bagby is supported by NIH National Institute of Child Health & Human Development grant RO1HD042570.

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Authors and Affiliations

  1. Developmental Origins of Health and Disease Division, University of Southampton, Southampton, UK

    David JP Barker

  2. Department of Medicine, Heart Research Center, Oregon Health & Sciences University, Portland, OR, USA

    David JP Barker

  3. Department of Medicine, Heart Research Center, Oregon Health & Sciences University, Portland, OR, USA

    Susan P Bagby

  4. Director of the Developmental Origins of Health and Disease Division, University of Southampton, Southampton, UK

    Mark A Hanson

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  1. David JP Barker
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Correspondence to David JP Barker.

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Barker, D., Bagby, S. & Hanson, M. Mechanisms of Disease: in utero programming in the pathogenesis of hypertension. Nat Rev Nephrol 2, 700–707 (2006). https://doi.org/10.1038/ncpneph0344

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