1. Inhibitors of the
angiotensin converting enzyme (ACE) have been shown to exert their cardioprotective actions through a
kinin-dependent mechanism. ACE is not the only
kinin degrading
enzyme in the rat heart. 2. Since
aminopeptidase P (APP) has been shown to participate in myocardial
kinin metabolism to the same extent as ACE, the aims of the present study were to investigate whether (a) inhibition of APP leads to a reduction of
myocardial infarct size in a rat model of acute ischaemia and reperfusion, (b) reduction of
infarct size is mediated by
bradykinin, and (c) a combination of APP and ACE inhibition leads to a more pronounced effect than APP inhibition alone. 3.
Pentobarbital-anaesthetized rats were subjected to 30 min left coronary artery occlusion followed by 3 h reperfusion. The APP inhibitor
apstatin, the
ACE-inhibitor ramiprilat, or their combination were administered 5 min before ischaemia. Rats receiving
HOE140, a specific
B(2) receptor antagonist, were pretreated 5 min prior to
enzyme inhibitors.
Myocardial infarct size (IS) was determined by tetrazolium staining and expressed as percentage of the area at risk (AAR). 4. IS/AAR% was significantly reduced in rats that received
apstatin (18+/-2%),
ramiprilat (18+/-3%), or
apstatin plus
ramiprilat (20+/-4%) as compared with those receiving saline (40+/-2%), HOE (43+/-3%) or
apstatin plus
HOE140 (49+/-4%). 5.
Apstatin reduces IS in an in vivo model of acute myocardial ischaemia and reperfusion to the same extent than
ramiprilat. Cardioprotection achieved by this selective inhibitor of APP is mediated by
bradykinin. Combined inhibition of APP and ACE did not result in a more pronounced reduction of IS than APP-inhibition alone.