Developmental programming of hypertension: insight from animal models of nutritional manipulation.

Hypertension is a multi-factorial disorder thought to result from both genetic and environmental factors. Epidemiological studies suggest that cardiovascular diseases such as hypertension may be programmed in-utero. Experimental studies demonstrate that developmental programming occurs in response to a nutritional insult during fetal life and leads to slow fetal growth and permanent structural and pathophysiological changes that result in the development of hypertension and cardiovascular disease. A reduction in nephron number, hyperfiltration and increased susceptibility to renal injury, activation of the sympathetic and renin angiotensin systems, in addition to, increases in oxidative stress, are potential mediators of post-natal hypertension programmed in response to developmental insult. However, the quantitative importance and integration of these mechanistic pathways has not been clearly elucidated. Additionally, animal models of developmental programming exhibit sex differences with severity of the fetal insult critical to the phenotypic outcome. Recent studies suggest that sex hormones may play a critical role via modulation of the normal regulatory systems involved in the long-term control of arterial pressure. Investigation into sex differences in the developmental programming of hypertension may provide critical insight into the mechanisms linking sex hormones and factors important in blood pressure regulation. Understanding the complexity of the developmental programming of adult disease may lead to preventive measures and early detection of cardiovascular risk.