Angiotensin-converting enzyme inhibitors were introduced as antihypertensive agents. However, they have been shown convincingly to decrease mortality in patients with congestive heart failure by reducing pre-load, after-load and systolic wall stress, thus resulting in increased cardiac output without an increase in heart rate (32- 35). Large clinical trials have also indicated that ACE inhibitors reduce mortality and reduce ventricular dysfunction after acute myocardial infarction (36- 37), limiting left ventricular remodeling as well as myocardial ischemic events. More recently, the HOPE study clearly demonstrated that the ACE inhibitor ramipril significantly lowered the risk of major cardiovascular outcomes by 25% to 30% in a large cohort of high-risk patients (38). Interestingly, the risk reduction for cardiovascular events was greater than would be expected from the observed mean difference in BP between groups, which suggests that the effects of ACE inhibition in this study were greater than could be attributed to its effect on lowering BP. We hypothesize that the cardioprotective effects of ACE inhibitors could, at least in part, be a consequence of the ability of endogenous bradykinin to initiate both classic and delayed PC effects. Moreover, some ACE inhibitors have been shown to exert direct infarct-limiting effects in experimental models, independent of their ability to augment PC (10,12,39- 40). Indeed, in this study, treatment with perindoprilat, which has a long biological half-life, 24 h before infarction resulted in a small, although non-significant, protective effect. The infarct-limiting effects of short-term administration of perindoprilat during the infarct-associated coronary occlusion may warrant further investigation.