ACE inhibitor

The body has a hormone system that, when triggered, tightens blood vessels and raises blood pressure. A key step in that chain is an enzyme that activates a powerful vessel-squeezing hormone. An ACE inhibitor blocks that enzyme, so the squeezing signal is never fully made and vessels stay relaxed.

The target is angiotensin-converting enzyme (ACE), a zinc-dependent peptidase that clips two amino acids off angiotensin I to make the potent vasoconstrictor angiotensin II. ACE inhibitors are designed to fit ACE's active site and reach toward its catalytic zinc ion with a zinc-binding group such as a carboxylate, sulfhydryl, or phosphinate, holding the enzyme shut.

Captopril, the first oral member, used a thiol to grip the zinc; later agents such as enalapril and lisinopril replaced the thiol with a carboxylate to improve tolerability. Many are ester prodrugs (enalapril becomes active enalaprilat after hydrolysis) for better absorption. They are mainstays for hypertension, heart failure, and protecting the kidneys in diabetes.

An honest caveat: by also slowing the breakdown of the peptide bradykinin, ACE inhibitors can cause a dry cough in some people and, rarely, swelling called angioedema.