Fetal Undernutrition and the Programming of Blood Pressure

For the last decade there has been considerable interest in the possibility that undernutrition during fetal development may exert long-term effects on cardiovascular physiology, effectively predisposing the individual to hypertension and coronary heart disease. These epidemiological observations have been developed into the developmental origins of health and disease (DOHAD) hypothesis. The DOHAD hypothesis is based upon an extensive range of ecological and retrospective cohort studies of human populations. Due to the problems associated with modelling a dietdisease association over periods of 50-60 years and the large number of confounders that may act within such a period, the epidemiological studies have often been inconsistent and the hypothesis subjected to robust criticism. A broad range of animal models of developmental programming have been established to provide evidence of the biological plausibility of DOHAD, to refine the hypothesis and, more importantly, are the focus of studies that are investigating the mechanisms that link poor maternal nutrition in pregnancy with long-term disease in the resulting offspring. This review considers nutritional programming of kidney development as a critical step in the development of non-essential hypertension and explores the involvement of the renin-angiotensin system, angiotensin receptors, glucocorticoids and epigenetic mechanisms in the association between fetal undernutrition and disease in adult life.