Mechanisms of Fetal Programming of Adult Hypertension

Abstract

Epidemiological and experimental studies suggest that the in utero environment plays a critical role in the development of adult disease, including cardiovascular disease and hypertension. Intrauterine growth retardation produced by maternal undernutrition or exposure to maternal glucocorticoids during critical periods of organogenesis impairs fetal growth and produces offspring that develop hypertension early in life.1 This concept of “fetal programming” was first proposed by Barker et al2 to describe the relationship between low birth weight and subsequent risk for the development of cardiovascular disease and hypertension, insulin resistance, and type 2 diabetes mellitus in adult life. Several studies have confirmed and extended the Barker et al2 hypothesis to fetal programming of Parkinson’s disease, dementia, osteoporosis, and polycystic ovary syndrome.3 Although most clinical and experimental studies support the role for fetal programming of adult hypertension, there is still controversy regarding the cause and mechanisms underlying this phenomenon. Studies to date implicate reduced nephron endowment, factors that affect endothelial and arterial compliance, alterations in the function of renin-angiotensin system (RAS), and programming of the major organs and endocrine/neural systems involved in long-term blood pressure regulation.1 Despite intense investigation into the mechanisms underlying fetal programming of adult hypertension, there is still no unifying hypothesis on how these different mechanisms and pathways are programmed in utero and how they ultimately result in dysregulation of blood pressure later in life. It is well documented that premenopausal women exhibit a lower incidence of cardiovascular disease and hypertension compared with age-matched …