Rationale for ACE inhibition as an anti-ischaemic therapy.
Research has established endothelial dysfunction as a pathophysiological mechanism underlying many cardiovascular disease processes. Tissue angiotensin-converting enzyme (ACE) plays a central role in regulating processes that contribute to endothelial function and cardiovascular disease. A number of large clinical studies have demonstrated conclusively the beneficial effects of ACE inhibition in patients with myocardial ischaemia and left ventricular dysfunction, including a significant reduction in the risk of recurrent myocardial infarction. Mechanistic findings from these studies indicated that the beneficial effects of ACE inhibition would extend to patients with preserved left ventricular function. Available results suggest that ACE inhibition with quinapril improves endothelial function in large and small vessels in patients with coronary artery disease and preserved left ventricular function. Quinapril also inhibits progression of coronary atherosclerosis in patients with high levels of low-density lipoprotein cholesterol (> or = 130 mg.dl-1) and reverses the toxic effects of smoking on endothelial function. Endothelial dysfunction also may be an important mechanism in episodes of angina and silent ischaemia. The central role of tissue ACE in endothelial function suggests that ACE inhibition has antiischaemic effects. A study in progress, the QUinapril Antiischaemia and Symptoms of Angina Reduction trial, addresses shortcomings in earlier studies of ACE inhibition for ischaemia and is expected to define the role of quinapril in ischaemia.
Pepine
C J
CJ
University of Florida College of Medicine, Gainesville 32610-0277, USA.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000401:mortality; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000401:mortality; D000077583:Quinapril; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D008078:Cholesterol, LDL; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril