Spirapril and Cilazapril Inhibit Neointimal Lesion Development but Cause no Detectable Inhibition of Lumen Narrowing After Carotid Artery Balloon Catheter Injury in the Rat
- 1 January 1993
- journal article
- research article
- Published by Informa UK Limited in Blood Pressure
- Vol. 2 (4), 322-331
- https://doi.org/10.3109/08037059309077175
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Multicenter European Research Trial with Cilazapril after Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group.Circulation, 1992
- Suppression of the vascular response to injury: The role of angiotensin-converting enzyme inhibitorsJournal of the American College of Cardiology, 1991
- A paradigm for restenosis based on cell biology: Clues for the development of new preventive therapiesJournal of the American College of Cardiology, 1991
- Long-Term Results of Coronary Balloon AngioplastyAnnual Review of Medicine, 1991
- The Proliferative Response to Vascular Injury Is Suppressed by Angiotensin-Converting Enzyme InhibitionJournal of Cardiovascular Pharmacology, 1990
- Prevention of restenosis after coronary angioplasty: A pharmacological approachEuropean Heart Journal, 1989
- Influence of inflation pressure and balloon size on the development of intimal hyperplasia after balloon angioplasty. A study in the atherosclerotic rabbit.Cell Metabolism, 1989
- Inhibitors of Angiotensin-Converting Enzyme Prevent Myointimal Proliferation After Vascular InjuryScience, 1989
- Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia.Cell Metabolism, 1989
- Kinetics of cellular proliferation after arterial injury. IV. Heparin inhibits rat smooth muscle mitogenesis and migration.Circulation Research, 1986