Alexander Research Summary

Hypertension is a multi-factorial disorder thought to result from both genetic and environmental
factors. However, numerous epidemiological studies report an inverse relationship between birth
weight and blood pressure suggesting that an increased risk of cardiovascular disease and
hypertension may also be consequence of poor fetal growth and low birth weight.

Within the United States, a higher percentage of low birth weight babies are born relative to
other Western countries with the highest rates of low birth weight localized in the Southern
states; higher rates of hypertension and cardiovascular disease are also concentrated in the South.

Our laboratory uses a unique model of placental insufficiency to investigate the mechanisms
linking low birth weight and hypertension. A reduction in nephron number, hyperfiltration and
increased susceptibility to renal injury, activation of the sympathetic and renin angiotensin
systems are potential mediators of post-natal hypertension programmed in response to
developmental insult. However, the quantitative importance and integration of these mechanistic
pathways in the developmental programming of hypertension has not been clearly elucidated.

Moreover, sex differences are observed in our model of programmed hypertension, and recent
studies from our laboratory suggest that their effects may not be direct, but may influence blood
pressure via modulation of regulatory systems critical to the long-term control of blood pressure.
Understanding the complexity of the developmental programming of adult disease may lead to
preventive measures and early detection of cardiovascular risk and help define the role of sex
hormones in mediating sexual dimorphism in response to a suboptimal fetal environment.