NEOINTIMA FORMATION IN INJURED HAMSTER CAROTID-ARTERY IS EFFECTIVELY PREVENTED BY THE COMBINATION G4120 AND QUINAPRIL

The prevention of neointima formation by the tissue selective angioten sin converting enzyme (ACE) inhibitor quinapril and by the combination quinapril/G4120 (a platelet alpha(IIb)beta(3) and smooth muscle cell alpha(v) beta(3) antagonist) was investigated in a hamster carotid art ery injury model. Quinapril at 10 mg/kg/day reduced neointima formatio n by about 45%, 1 and 2 weeks after injury to the artery, i.e. signifi cantly better than the non-tissue selective ACE inhibitor captopril at 100 mg/kg/day. Quinapril did not decrease the early smooth muscle cel l (SMC) proliferation in the media, but in agreement with its inhibiti on of the carotid artery ACE activity by 62%, SMC proliferation was re duced by 70% in the newly forming intima. To improve the inhibition of early medial SMC proliferation, quinapril (10 mg/kg/day) was compleme nted with G4120 (100 mu g/kg/h). This combined treatment reduced the p roliferation of medial SMCs to about 50% throughout the first week fol lowing injury, whereas intima SMC proliferation was reduced by 70% thr oughout treatment. Accordingly, the drug combination reduced neointima formation more potently than each drug separately by 70%. The disrupt ion of medial elastic laminae, observed in the control and G4120 treat ed group, was consistently reduced when G4120 was complemented with qu inapril. Thus, the present study shows in a hamster model of carotid a rtery injury, that combining drugs that prevent SMC migration and prol iferation via different modes of action can lead to the effective prev ention of neointima formation.