The overall hypothesis of our study is that ACE2 is an important element of the brain RAS, modulating the levels of central Ang-II available to stimulate neuronal AT1 receptors localized in cardiovascular control centers; inhibition of ACE2 may be involved in the pathogenesis of hypertension. We are using genetically-engineered mice and molecular, physiological, and pharmacological techniques to investigate the role of ACE2 in the regulation of blood pressure. During the 2004 SROP fellowship, it was our goal in this project to begin examining the role of ACE2 in the brain of mice and how it is affected by changes in brain RAS. In 2003, Gallagher et al reported that ACE2 in astrocytes is down-regulated by Ang-II. Our objective was to examine ACE2 in the brain of non-transgenic (NT) mice and determine whether it is modulated with genetic alteration of RAS.