ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS POTENTIATE PRECONDITIONING THROUGH BRADYKININ B-2 RECEPTOR ACTIVATION IN HUMAN HEART

Objectives. This study was designed to determine whether angiotensin c onverting enzyme (ACE) inhibitors play a role in cardioprotection in a human model of preconditioning. Background. Recent studies have sugge sted that bradykinin may contribute to the protective effects of preco nditioning in animal models. ACE inhibitors are known to inhibit the d egradation of bradykinin and hence may be able to potentiate the effec t of preconditioning. Methods. We examined the effects of the ACE inhi bitors captopril and lisinopril in combination with a subthreshold pre conditioning stimulus (i.e., insufficient to have any protective effec ts alone), Human atrial trabeculae were superfused with Krebs buffer a nd paced at 1 Hz, They were subjected to a full or subthreshold precon ditioning stimulus consisting of either 3 or 1.5 min of simulated isch emia and 7 min of reoxygenation, In each instance, this stimulus was f ollowed by 90 min of simulated ischemia and 2 h of reoxygenation. In a ddition, the subthreshold preconditioned group had 20 min of previous ACE inhibitor treatment. Results. Recovery of contractile function (pe rcent of baseline) was 22 +/- 1% (mean +/- SEM) in the control group v ersus 61 +/- 1% in the preconditioned group, The subthreshold precondi tioned group and the ACE inhibitor alone groups did not exhibit any pr otection; 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 diffe rence between these values and recovery after the full preconditioning stimulus. Furthermore, Hoe 140, a specific bradykinin B-2 receptor an tagonist, abolished the protection. Conclusions. To our knowledge, the se are the first results in human muscle to suggest that ACE inhibitor s may augment ischemic preconditioning, possibly through B-2 receptor activation. (C) 1997 by the American College of Cardiology.