Angiotensin-converting enzyme inhibitors: mechanistic controversies.

Many studies have investigated the mechanisms responsible for the therapeutic effects of the angiotensin converting enzyme inhibitors. Initially, the hemodynamic changes that occur with these agents were attributed solely to the inhibition of the renin-angiotensin-aldosterone system in plasma. Further research suggested other mechanisms were operable as a relationship was not always evident between hemodynamic changes and inhibition of the plasma renin-angiotensin-aldosterone system. A relationship between the pharmacodynamics of these agents and the inhibition of vascular and tissue renin-angiotensin systems, however, has been observed. Mechanisms less likely to contribute to the actions of the angiotensin converting enzyme inhibitors are increases in bradykinin and prostaglandin concentrations, or inhibition in the renin-angiotensin system within the central nervous system. Ancillary cardiovascular effects of angiotensin converting enzyme inhibitors offer possible new therapeutic gains. An understanding of these mechanistic controversies and newly-defined cardiovascular actions of angiotensin converting enzyme inhibitors are important to clinicians using these agents.