icatibant and moexipril

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 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.. We compared the effects 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 icatabant was used to investigate the role of bradykinin in the cardioprotective effects of ACE inhibition. Rats underwent a sham operation or surgery to induce myocardial infarction. Treatment was started 1 week before myocardial infarction and continued for another 6 weeks after the procedure.. Moexipril reduced infarct size (100 +/- 9mm2 compared with 165 +/- 8mm2), 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 +/- 1.5 mmHg compared with 14.0 +/- 1.7 mmHg). All of these effects of the ACE inhibitor were blocked by concomitant treatment with icatibant. Losartan did not affect any of these cardiac parameters.. 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.

Topics: Adrenergic beta-Antagonists; Analysis of Variance; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Biphenyl Compounds; Bradykinin; Disease Models, Animal; Heart; Heart Failure; Hemodynamics; Imidazoles; Isoquinolines; Losartan; Male; Myocardial Contraction; Myocardial Infarction; Myocardium; Organ Size; Rats; Rats, Wistar; Tetrahydroisoquinolines; Tetrazoles