Angiotensin-converting enzyme inhibitors potentiate preconditioning through bradykinin B-2 receptor activation in human heart

Objectives. This study was designed to determine whether angiotensin converting enzyme (ACE) inhibitors play a role in cardioprotection in a human model of preconditioning. Background. Recent studies have suggested that bradykinin may contribute to the protective effects of preconditioning in animal models. ACE inhibitors are known to inhibit the degradation of bradykinin and hence may be able to potentiate the effect of preconditioning. Methods. We examined the effects of the ACE inhibitors captopril and lisinopril in combination with a subthreshold preconditioning stimulus (i.e., insufficient to have any protective effects alone), Human atrial trabeculae were superfused with Krebs buffer and paced at 1 Hz, They were subjected to a full or subthreshold preconditioning stimulus consisting of either 3 or 1.5 min of simulated ischemia and 7 min of reoxygenation, In each instance, this stimulus was followed by 90 min of simulated ischemia and 2 h of reoxygenation. In addition, the subthreshold preconditioned group had 20 min of previous ACE inhibitor treatment. Results. Recovery of contractile function (percent of baseline) was 22 +/- 1% (mean +/- SEM) in the control group versus 61 +/- 1% in the preconditioned group, The subthreshold preconditioned group and the ACE inhibitor alone groups did not exhibit any protection; however, in combination, the protection was significant (71 +/- 4% in the captopril group, 58 +/- 8% in the lisinopril group, p < 0.005) compared with the control group. There was no significant difference between these values and recovery after the full preconditioning stimulus. Furthermore, Hoe 140, a specific bradykinin B-2 receptor antagonist, abolished the protection. Conclusions. To our knowledge, these are the first results in human muscle to suggest that ACE inhibitors may augment ischemic preconditioning, possibly through B-2 receptor activation. (C) 1997 by the American College of Cardiology.