Examining the renin-angiotensin system one hundred years after its discovery

This article reviews the biology of angiotensin converting enzyme (ACE). There are two ACE isozyme, somatic ACE (made by tissues such as the lung and kidney) and testis ACE (produced only by developing male germ cells). Mice lacking all ACE expression were prepared using homologous recombination of embryonic stem cells. These animals have profoundly low blood pressures, reduced male fertility and a renal lesion characterized by under development of the renal medulla and papilla. A second line of mice was made in which ACE activity is found in the plasma but is absent from all tissues such as lung. These animals have a phenotype very similar to mice lacking all ACE with the exception of the renal lesion which is much less pronounced. This second line of mice strongly suggests that it is tissue-bound ACE which is critical in the proper functioning of the renin-angiotensin system.