Angiotensin converting enzyme (ACE) inhibitors are agents used to relax blood vessels and lower blood pressure. They prevent an enzyme from producing angiotensin II, which narrows blood vessels and raises blood pressure, meaning the heart has to work harder to pump blood around the body.

ACE inhibitors are prescribed to treat or prevent symptoms in conditions such as coronary artery disease, hypertension, kidney disease, heart attack, heart failure and migraines. These drugs may be prescribed in combination with other antihypertensive drugs such as diuretics or calcium channel blockers and they are usually taken once a day, in the morning.

ACE inhibitors work by decreasing the activity of the renin-angiotensin-aldosterone system (RAAS). The RAAS is a complex physiological system that controls fluctuations in blood pressure. A protein called renin is released by the juxtaglomerular apparatus in the kidneys. Renin then produces angiotensin, the active form of which stimulates the adrenal gland to produce a hormone called aldosterone. Aldosterone stimulates the reabsorption of water and conservation of sodium, therefore increasing water retention and blood pressure.

The RAAS is activated when blood pressure falls or when a disruption of the salt-water balance is indicated by a low blood volume or a low concentration of sodium in the kidney, for example. Renin released by the kidneys cleaves the first ten amino acids present on the angiotensin protein. These cleaved residues are referred to as angiotensin I, which is converted by ACE into angiotensin II through the removal of a further two amino acids. Angiotensin II is the potent, active form of angiotensin that can stimulate aldosterone release.

ACE inhibitors block the conversion of angiotensin I to angiotensin II and the effects of angiotensin II are therefore prevented. This competitive inhibition of ACE to prevent the formation of angiotensin II occurs in the kidney, blood vessels, heart, brain and adrenal gland This leads to an increase in the amount of sodium and urine excreted, reduced resistance in kidney blood vessels, an increase in venous capacity and decreases in cardiac output, stroke work and volume.

ACE inhibitors have an increasing role in the management of cardiovascular risk. Examples of these drugs include enalapril, captopril, fosinopril, perindopril, lisinopril, ramipril and quinapril. The reduction in blood pressure that follows ACE inhibition is greatest after stimulation of the RAAS system due to diuretic therapy, for example, but these agents can also reduce blood pressure activity when RAAS activity is low or normal. However, people with low renin hypertension such as elderly people or Afro-Caribbeans tend to be less responsive to ACE inhibitor therapies.

Practical concerns

At low doses, the dose-blood pressure response relationship of ACE inhibitors is linear, but quickly plateaus within the therapeutic range. Peak reduction in blood pressure is not achieved through further increases in dose, but the duration of action is prolonged. The reduced blood pressure following ACE inhibition does not alter the heart rate or cause reflex tachycardia.

ACE inhibitors differ in their duration of action and efficacy and some types are not suitable for only taking once daily. In the case of enalpril, twice daily administration is required for a consistent response. The shortest duration of action is seen with captopril, which has to be taken two or three times a day if blood pressure is going to be reduced over 24 hours. With most ACE inhibitors, the duration of lowered blood pressure is dose-dependent and to achieve a consistently reduced blood pressure, the maximum recommended dose should be administered. However, to reduce the risk of dangerous initial falls in blood pressure among elderly individuals or those with impaired renal function or heart failure, low dosages are generally recommended at the beginning of treatment.