Section Review Cardiovascular & Renal: Bradykinin degradation: potential pathways for cardiovascular therapeutic use

Abstract

Bradykinin (BK) is a widely distributed nine amino acid peptide with potent cardiovascular effects. Physiologically, BK has a very brief duration of action due to rapid metabolism by a number of widely distributed enzymes, including carboxypeptidase N, angiotensin converting enzyme (ACE), endopeptidase 24.11 (EP24.11), en-dopeptidase 24.15 (EP24.15), and aminopeptidase P. The physiological importance of BK in cardiovascular regulation is beginning to be recognised, due to the development of inhibitors of these BK-degrading enzymes. ACE inhibitors have been used in clinical practice for a number of years for the treatment of cardiovascular diseases, but it has only been recognised recently that their beneficial effects are due to preservation of endogenous BK from metabolism, as well as by prevention of angiotensin II production. Inhibitors of EP24.11 have been tested in various animal models of cardiovascular diseases, and in human patients, and have been shown to have limited benefit when given alone. Wh...