By Dr Ananya Mandal, MD
Angiotensin-converting enzyme (ACE) inhibitors are drugs that are mainly used to treat high blood pressure and congestive heart failure. These agents are also useful in patients with diabetic kidney damage.
The first stage in the development of these drugs was the isolation of ACE in plasma by Leonard T. Skeggs and his research fellows in 1956. In 1965, a scientist called Sergio Ferreira reported the presence of bradykinin potentiating factors in the South American pit viper ( Bothrops jararaca). Ferreira suggested that the conversion of inactive angiotensin I to active angiotensin II occurred in the plasma but in 1967, research by scientists John Vane and Kevin K.F. Ng showed that plasma ACE was shown to be too slow to account for this conversion. Further research showed that the conversion does not occur in the plasma but while ACE is being passed through the pulmonary circulation.
Bradykinin is inactivated in circulating blood and eliminated completely by passage through the pulmonary circulation. Angiotensin I is also eliminated at this point due to its conversion to angiotensin II. This bradykinin inactivation and angiotensin I conversion was originally thought to be achieved by the same enzyme but further experiments by Ng and Vane in 1970 showed that the conversion of angiotensin I to angiotensin II is inhibited on passing through the pulmonary circulation. Peptide analogues were used by David Cushman, Miguel Ondetti and colleagues to research the structure of ACE and this led to the development of the first orally-active ACE inhibitor captopril in 1975.
Reviewed by Sally Robertson, BSc
Last Updated: Sep 10, 2014