The use of knockout mouse technology to achieve tissue selective expression of angiotensin converting enzyme

The resin angiotensin system (RAS) plays an essential role in blood pressure regulation and electrolyte homeostasis. The effecter peptide of the RAS, angiotensin II, is produced by angiotensin converting enzyme (ACE) in multiple tissues. Genetic deletion of ACE in mice resulted a phenotype of low blood pressure, anemia and kidney defects. However, it is not clear whether the lack of the systemic or the local production of angiotensin II caused these defects. To understand the role of local angiotensin II production, we developed a method to achieve tissue specific ACE expression through homologous recombination. In this review, we discuss mouse models in which endothelial ACE was eliminated and replaced by hepatic ACE. These studies suggest that both circulating angiotensin II and local angiotensin II production play a role in angiotensin II generation; the elimination of local angiotensin II generation up-regulates systemic production and maintains physiologic homeostasis.