Spirapril and cilazapril inhibit neointimal lesion development but cause no detectable inhibition of lumen narrowing after carotid artery balloon catheter injury in the rat.
Five groups of 12 rats were subject to balloon lesion of the left carotid artery and neointimal thickening was measured histologically 2 weeks after injury. Rat groups received either spirapril (3, 10 or 30 mg/kg/day, administered throughout the study in the food), cilazapril (10 mg/kg/day) or placebo. Spirapril caused a dose-dependent inhibition of the neointimal thickening of the rat carotid artery. The degree of inhibition with 10 mg/kg/d spirapril and cilazapril was similar (-44% and -42% respectively). The carotid lumen area was measured in vivo by nuclear magnetic resonance (NMR) imaging both before and 2 weeks after balloon injury and also postmortem by histological techniques. Two weeks after injury, the lumen area of the left carotid artery was significantly reduced following balloon injury, as measured by both techniques. Treatment did not detectably modify this stenosis process despite the use of two independent methods for assessing lumen size, even though neointimal thickening was strongly attenuated by both angiotensin converting enzyme inhibitors. This dissociation between inhibition of neointimal lesion development and decrease of lumen size provides a new view of the role of angiotensin converting enzyme inhibitors in vascular damage situations. Our results suggest that the focus, particularly in clinical studies, on lumen size, may mean that potentially beneficial effects of these drugs on other parts of the vascular wall be overlooked.
Cook
N S
NS
Sandoz Pharma Ltd., Basel.
Zerwes
H G
HG
Pally
C
C
Rudin
M
M
Hof
R P
RP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries; D002404:Catheterization / Q000009:adverse effects*; D017315:Cilazapril / Q000494:pharmacology*; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006651:Histocytochemistry; D008279:Magnetic Resonance Imaging; D051381:Rats; D017208:Rats, Wistar; D016707:Tissue Fixation
D000806:Angiotensin-Converting Enzyme Inhibitors; D017315:Cilazapril; D004656:Enalapril; C052555:spirapril