ACE INHIBITORS (angiotensin-converting enzyme inhibitors) act by inhibiting the enzyme EC, variously known as angiotensin-converting enzyme (ACE), kininase II, dipeptidyl peptidase A. This peptidase, found in vascular endothelial cells and plasma, converts, by carboxyterminal dipeptidyl cleavage, the circulating vascular hormone angiotensin from its inactive decapeptide form angiotensin I, to the active octapeptide form, angiotensin II. Since angiotensin II is a very potent vasoconstrictor, the effect of ACE inhibitors is to cause vasodilatation with an overall hypotensive effect. Such drugs can be used as ANTIHYPERTENSIVES, and also in HEART FAILURE TREATMENT. However, drugs of this class have a number of side-effects (in particular an irritating cough), some of which can be attributed to the fact that ACE inhibitors necessarily prolong the duration of action of, and so potentiate, bradykinin. This sensory nerve activator and hypotensive hormone is degraded to an inactive dipeptidyl cleavage product by the same enzyme (in the kinin context commonly referred to as kininase II).

ACE inhibitor drugs were developed by modelling interaction with the active site of the enzyme of a snake-venom-derived bradykinin-potentiating peptide, and from this the necessary structure of non-peptide inhibitors was inferred. The first such ACE inhibitor used medicinally was captopril. Later examples in clinical use include: cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril. Several ACE inhibitors are now administered clinically as prodrugs — which have good bioavailability, but are inactive in their own right. They are then converted to the active molecule in vivo, usually by esterases (e.g. enalapril to enalaprilat, and ramipril to ramiprilat).