Angiotensin-converting enzyme (ACE) inhibitors are drugs mainly used to treat high blood pressure and congestive heart failure. Further examples of conditions that are treated with these drugs include the following:
- Coronary artery disease
- Certain chronic kidney diseases
- Heart attack
ACE inhibitors work by preventing the production of angiotensin II, a chemical that causes blood vessels to narrow once it enters the bloodstream. The blood then has less space to move in, thereby raising the blood pressure. Angiotensin II also triggers the release of a hormone called aldosterone, which increases the amount of water the body retains. This increase in bodily fluid along with restricted space causes the blood pressure to rise.
ACE inhibitors reduce the level of angiotensin II, which allows the blood vessels to relax and dilate so that the blood pressure falls. The ACE inhibitor competitively inhibits the activity of ACE, which stops active peptide angiotensin II being formed from the inactive angiotensin I. The greatest fall in blood pressure is seen when ACE inhibitors are administered after the renin-angiotensin system is stimulated such as during renal artery stenosis or diuretic therapy. However, these drugs are also used to lower blood pressure when renin-angiotensin system activity is normal or low.
There are various different types of ACE inhibitors, with the main difference between them being how long the effects last. Some of these drugs are short-acting and others are long-acting. Long-acting ACE inhibitors can be taken less often throughout the day than short-acting forms. An example of a long-acting ACE inhibitor is perindopril, which only needs to be taken once a day. Captopril is an example of a short-acting ACE inhibitor that is taken three time a day. Further examples of ACE inhibitors include the following:
- Benazepril (Lotensin)
- Lisinopril (Zestril)
- Enalapril (Vasotec)
- Ramipril (Altace)
- Moexipril (Univasc)
- Quinapril (Accupril)
- Trandolapril (Mavik)
The majority of people who take ACE inhibitors do not experience side effects. However, the most common side effect associated with the use of ACE inhibitors is a dry, irritating and persistent cough. Other potential side effects include the following:
- Changes in sense of taste
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.