Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. Lastly, N- and C-domain selective ACE inhibitors have led to new uses for ACE inhibitors.