Abstract
Despite how common hypertension is in children, adolescents, and adults, the antecedent mechanisms underlying its origins remain incompletely understood. Increasingly strong evidence from clinical, epidemiological, and preclinical studies support the concept of early-life programming of hypertension within the framework of the developmental origins of health and disease theory. In essence, harmful antenatal exposures cause the fetus (and the intrauterine environment) to alter its physiological, structural, and metabolic development to adapt to this deleterious environment to improve short-term survival. However, if of sufficient severity, number, timing, or duration, such exposure-induced developmental plasticity can program persistent, maladaptive cardiovascular phenotypes that appear later on over the life course and ultimately increase the risk of developing hypertension. Well-described antenatal exposures can come from a variety of sources – maternal, paternal, fetal, and environmental – and can occur throughout pregnancy, from gametogenesis through birth. These exposures include abnormal maternal-fetal vascular supply and nutrient delivery (both restricted and excess), maternal stress causing increased exposure to endogenous glucocorticoids, inflammation, and exogenous exposures. Programming mechanisms can occur directly or indirectly via placental insufficiency and/or growth restriction; they likely do not simply occur due to low birth weight in isolation. Programming alters organ structure and function, tissue cell type, number, and distribution, blood supply, and hormonal system enzyme, substrate, and receptor expression and function in a variety of cardiovascular tissues including the kidneys, brain, vasculature, and heart. Additional factors further contribute to the programming of hypertension, including epigenetic changes as well as preconception and postnatal exposures. This chapter reviews the preclinical evidence for antenatal factors that result in programmed hypertension, including the complex interactions among these mechanisms, and highlights gaps in the field that limit translation to patient care. Understanding these programming factors has important implications for primordial prevention and treatment strategies.
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South, A.M. (2023). Antenatal Programming of Blood Pressure. In: Flynn, J.T., Ingelfinger, J.R., Brady, T.M. (eds) Pediatric Hypertension. Springer, Cham. https://doi.org/10.1007/978-3-031-06231-5_57
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