ACE Inhibitors: Pharmacology

Abstract

More than IS inhibitors of the angiotensin-converting enzyme (ACE) are now clinically available worldwide. ACE inhibitors can be divided into three chemical classes according to their zinc ligand. They mainly differ in their elimination half-life, potency, lipophilicity and the route of elimination. ACE inhibitors act by blocking the systemic and local generation of angiotensin II (Ang II) from angiotensin I (Ang I) and by inhibiting the degradation of kinins. Experimental studies have shown that both actions of the ACE inhibitors are important for their antihypertensive and organ-protective actions. ACE inhibitors effectively lower blood pressure and prevent or reverse the hypertension-in duced cardiac and vascular structural changes. In addition, ACE inhibitors can improve cardiac function and prevent cardiac remodelling in animals with experimentally induced heart failure and are beneficial when administered at various time points before and after myocardial infarction. ACE inhibitors can effectively prevent or regress endothelial dysfunction, induced, for example, by high blood pressure, and exert antiatherosclerotic effects. Inhibition of the local formation of proinflammatory Ang II has been shown to be a promising therapeutic approach to stabilize plaque and prevent its rupturing. Several studies have also revealed nephroprotective effects of ACE inhibitors. Finally, ACEinhibition improve insulin resistance and insulin sensitivity and reduce albuminuria and microalbuminuria in experimental models of diabetes mellitus . In summary, ACE inhibitors not only lower blood pressure but also positively influence a number of cardiovascular risk factors such as cardiac and vascular hypertrophy, endothelial dysfunction, atherosclerosis or insulin resistance. These effects help to explain their clinical benefit in heart failure, postmyocardial infarction, chronic renal insufficiency and diabetes mellitus