Developmental Programming of Hypertension: Physiological Mechanisms.

Abstract

Epidemiological studies indicate that the origins of high blood pressure initiates in fetal life.1–3 Recent reviews highlight a role for numerous factors in the pathogenesis of the developmental programming of hypertension including epigenetic processes, glucocorticoids, reduced nephron number, activation of the sympathetic nervous system, and the renin–angiotensin system (RAS) and endothelial dysfunction.4–7 Studies published in Hypertension and other journals highlight the complexity of cardiovascular risk that has its origins in fetal life. The purpose of this minireview is to present an update on recent studies in Hypertension that investigate the underlying mechanisms that contribute to the developmental programming of hypertension and increased risk for cardiovascular disease. Barker8 first proposed the theory of the fetal origins of coronary heart disease based on the hypothesis that adaptive responses by the fetus to maternal undernutrition would enhance survival to birth at the expense of later cardiovascular health. The first animal studies to investigate the Barker hypothesis utilized rodent models to demonstrate that maternal undernutrition during gestation programs an increase in blood pressure in the offspring.9 Based on previous studies indicating a role for the renal nerves in experimental models of low birth weight,10,11 Mizuno et al12 proposed that increased blood pressure in protein-restricted offspring would be associated with an increase in baseline measure of renal sympathetic nerve activity (SNA). Although baseline measurement of renal SNA under anesthesia did not differ in male protein-restricted offspring versus male control at 4 to 5 months of age, renal SNA was significantly elevated in response to a secondary hit of physical stress in association with a greater blood pressure response12 indicating a role for an increase in renal SNA in the developmental programming of increased blood pressure and cardiovascular risk. Chronic systemic blockade of …