Background: The beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the prevention of heart failure following myocardial infarction are widely accepted. However, the underlying mechanisms are still a matter of discussion. We therefore investigated the relative contribution of the inhibition of the breakdown of bradykinin and of the inhibition of angiotensin-II synthesis to the beneficial actions of ACE inhibitors in chronic heart failure following myocardial infarction.
Methods: We compared the effects of pretreatment with the ACE inhibitor moexipril with those of the type 1 angiotensin (AT1)-receptor antagonist losartan on structural and functional cardiac parameters after myocardial infarction in rats. In addition, the bradykinin B2-receptor antagonist icatibant was used to investigate the role of bradykinin in the cardioprotective effects of ACE inhibition. Rats underwent a sham operation or sugery to induce myocardial infarction. Treatment was started 1 week before myocardial infarction and continued for another 6 weeks after the procedure.
Results: Moexipril reduced infarct size (100 ± 9 mm2 compared with 165 ± 8 mm2), the ratio of total heart weight to body weight (2.6 ± 0.1 g/kg compared with 2.9 ± 0.1 g/kg) and end-diastolic pressure (8.2 ± 1.5mmHg compared with 14.0 ± 1.7mmHg). All of these effects of the ACE inhibitor were blocked by concomitant treatment with icatibant. Losartan did not affect any of these cardiac parameters.
Conclusion: The cardioprotective effects of the ACE inhibitor moexipril administered before myocardial infarction in the present study were a result of the reduced breakdown of kinins rather than of the reduced synthesis of angiotensin II.
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