Inhibition of converting enzyme and neointima formation after vascular injury in rabbits and guinea pigs.
Recently, it has been shown that cilazapril could suppress neointima formation after vascular injury in rats. The goal of the present study was to confirm these findings in guinea pigs and rabbits. Vascular injury was produced by ballooning the right carotid artery of guinea pigs and the right iliac artery of rabbits. The animals were treated with either placebo or cilazapril (30 mg/kg/day and 3 mg/kg/day in guinea pigs and rabbits, respectively). Cilazapril decreased by 42% (p less than 0.001) the neointima area in the guinea pig but was ineffective in rabbits. However, in rabbits, doses of cilazapril higher than 3 mg/kg could not be given because of known toxicological effects in the rabbit. We conclude that the protective effect of cilazapril described in rats also is observed in guinea pigs. However, in rabbits, the maximal tolerated dose of cilazapril was ineffective. These results underline the importance of ongoing clinical studies to evaluate if, in humans, cilazapril inhibits restenosis after coronary angioplasty.
Clozel
J P
JP
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Hess
P
P
Michael
C
C
Schietinger
K
K
Baumgartner
H R
HR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017315:Cilazapril; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D013045:Species Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril