Lessons from angiotensin-converting enzyme-deficient mice

Since the first description of renin by Tigerstedt and Bergman [1] in 1898, many papers have described the biochemistry and physiological roles of the reninangiotensin system [2]. A critical component of this system is angiotensin-converting enzyme (ACE), a peptidase which cleaves the inactive peptide angiotensin (Ang) I to generate the potent vasoconstrictor Ang II. This enzyme also cleaves other peptides, including bradykinin. Its activity increases blood pressure, and ACE inhibitors have become a mainstay in the treatment of hypertension and congestive heart failure. It has recently become possible to create mice which lack ACE. These mice have low systolic blood pressure, striking renal defects and reduced male fertility, phenotypes which emphasize the familiar roles of ACE and provide insight into unexpected functions of this enzyme.