Abstract :
Angiotensin II (ATII) is recognized as being important in the pathophysiology of hypertension and congestive heart failure. Recent evidence suggests that it might also be of importance in the pathophysiology of acute myocardial infarction.
ATII may play an important role in the development of endothelial dysfunction and atherosclerosis. ATII has recently been shown to oxydize low density lipoprotein-cholesterol, stimulate cytokines, and promote the migration of monocytes into the arterial wall. ATII may also play a role in coronary atherosclerotic plaque rupture. ATII causes the release of endothelin which may cause local coronary vasoconstriction and hence predispose to coronary atherosclerotic plaque rupture. ATII may also promote thrombosis after plaque rupture. ATII causes the release of plasminogen activator inhibitor, which in the presence of plaque rupture could impair intrinsic thrombolysis and promote thrombosis.
The potential importance of ATII in the pathophysiology of acute myocardial infarction has been emphasized by the finding of Alderman et al that renin is an independent risk factor for myocardial infarction in patients with hypertension as well as the finding of Cambien et al that the angiotensin converting enzyme DD genotype is associated with acute myocardial infarction, especially in patients without other known risk factors for coronary artery disease. The findings in the SOLVD and SAVE Trials in patients with systolic left ventricular dysfunction that angiotensin converting enzyme-inhibitors (ACE-I) are associated with a significant reduction in the incidence of acute myocardial infarction and recurrent ischemic events is further, although indirect, evidence for the role of ATII in the pathophysiology of acute infarction. Several large scale randomized trials including QUIET, HOPE, and PEACE should provide further information on the role of ACE-I in preventing infarction and improving survival in patients with ischemic heart disease. A more direct answer to the question of the importance of ATII in the pathophysiology of acute myocardial infarction will however come from studies of ATII type I receptor antagonists, since a beneficial role of ACE-I in preventing acute myocardial infarction could be due to inhibition of ATII formation and/or formation of bradykinin and release of NO.
