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Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide

  • Original Articles
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Annals of Vascular Surgery

Abstract

Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 ± 2.3%; group II (enalaprilat), 9.5 ± 0.7%; and group III (DMSO), 17.6 ± 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p<0.01, ANOVA, Student'sttest), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury. These results support the theory that the smooth muscle cell mitogen angiotensin II plays an important role in the proliferation of medial myofibroblasts following vascular injury.

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Authors and Affiliations

  1. Section of Vascular Surgery, UCLA School of Medicine, 10833 LeConte Ave., 90024, Los Angeles, CA

    Michael M. Law MD, Michael D. Colburn MD, George E. Hajjar MD, Hugh A. Gelabert MD, William J. Quiñones-Baldrich MD & Wesley S. Moore MD (Professor of Surgery, Chief)

Authors
  1. Michael M. Law MD
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  2. Michael D. Colburn MD
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  3. George E. Hajjar MD
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  4. Hugh A. Gelabert MD
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  5. William J. Quiñones-Baldrich MD
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  6. Wesley S. Moore MD
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Additional information

Supported in part by a grant from the Joash Foundation and the Veterans Administration.

We would like to acknowledge the support of Merck Sharp & Dohme of West Point, Pa., for generously supplying the enalaprilat (Vasotec I.V.) used in this study.

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Law, M.M., Colburn, M.D., Hajjar, G.E. et al. Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide. Annals of Vascular Surgery 8, 158–165 (1994). https://doi.org/10.1007/BF02018864

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