Intrauterine programming of hypertension: the role of the renin-angiotensin system

Abstract

From experiments with prenatal undernutrition in the rat, it is clear that fetal exposure to glucocorticoids of maternal origin is a key first step in the programming of hypertension and perhaps coronary heart disease. The chain of events leading from glucocorticoid action in the fetal tissues to hypertension in adulthood involves the development of hypersensitivity to glucocorticoids in adult life (Scheme 1). This has the effect of activating the RAS through induction of key genes such as ACE, which, in turn, may increase sensitivity of the blood vessels to the actions of ANGII. Another consequence of prenatal undernutrition, which may or may not involve glucocorticoids, is the abnormal development of the kidney [35]. Impaired nephrogenesis must surely have an impact upon lifelong renal function and cardiovascular control. Progress has been made in demonstrating that hypertension can be prenatally programmed through maternal dietary manipulation and some of the putative mechanisms involved have been identified. The priorities in this field of research must now be to clarify the role of maternal diet as a programming stimulus in order to generate an effective series of public health guidelines for pregnant women. Although the identification of metabolic mechanisms might suggest possible pharmacological interventions in early life as a means of reducing cardiovascular risk in adult life [49], it will always be more desirable to optimize maternal diet.