The brain renin-angiotensin system: localization and general significance

This report summarizes the present data about the existence of components of the renin-angiotensin system in the rat brain. Angiotensinogen mRNA, mas proto-oncogene mRNA, angiotensin II (Ang II), and Ang II receptors have been mapped in the brain by using in situ hybridization, immunocytochemistry, and receptor autoradiography. These markers turned out to be widely distributed throughout the brain and to be not only restricted to areas related to cardiovascular control, but also to be present in functionally different areas, suggesting also other functions of angiotensin peptides. The distribution patterns of these components were correlated with data on the distribution of angiotensinogen, renin, angiotensin converting enzyme, and angiotensin fragments that revealed substantial topological mismatches. Using the model of "volume transmission," possible explanations for these mismatches are proposed. In this regard, a possible involvement of angiotensin fragments and the mas proto-oncogene in the functioning of the brain renin-angiotensin system is also discussed, demonstrating the increasing complexity of this central regulatory system.