DEXAMETHASONE AND ENALAPRIL SUPPRESS INTIMAL HYPERPLASIA INDIVIDUALLYBUT HAVE NO SYNERGISTIC EFFECT

Vascular injury is associated with complex interactions that lead to d evelopment of intimal hyperplasia (IH). We have demonstrated previousl y that the corticosteroid dexamethasone and the ACE-inhibitor enalapri l are effective in suppressing the development of IH. We hypothesize t hat due to distinctly different pharmacologic mechanisms of action, a synergistic effect would be expected if these agents were given in com bination. Forty New Zealand White rabbits underwent balloon catheter d enudation of the carotid artery. Animals were divided into four equal treatment groups and received daily intramuscular injections: Group 1, saline; Group 2, enalapril 0.07 mg/kg, Group 3, dexamethasone 0.125 m g/kg; and Group 4, enalapril 0.07 mg/kg plus dexamethasone 0.125 mg/kg . Vessels were harvested at 12 weeks and intimal hyperplasia was measu red as a ratio of the absolute area of IH to the normalized area enclo sed by the internal elastic lamina (IH/IEL). Mean values for IH/IEL ar e expressed as a percent (SD): Group 1, 32.31 (14.9); Group 2, 9.47 (2 .11); Group 3, 5.40 (4.14); and Group 4, 8.49 (4.27). All treatment gr oups demonstrated significant suppression of IH compared to the contro l group (p<0.01); dexamethasone was more effective than enalapril (p = 0.01). There was no statistical difference in IH suppression between respective agents and the combination group (p>0.10). Coadministration of dexamethasone and enalapril provides no advantage over single-agen t therapy in suppressing the development of IH, suggesting that maxima l suppression is obtained with single-agent treatment or that these ag ents affect IH through a common pathway.