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

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Abstract
This Review integrates discussion of well-established mechanisms that are known to underlie the 'fetal origins hypothesis' of hypertension with examination of mechanisms for which data continue to emerge. Set in the context of implications for public health, the authors suggest that monitoring the blood pressure, renal function and body weight of at-risk children might help to reduce the likelihood of kidney and cardiovascular disease developing in later life. 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.