PHARMACOLOGICAL SUPPRESSION OF INTIMAL HYPERPLASIA - A DOSE-RESPONSE SUPPRESSION BY ENALAPRIL

Intimal hyperplasia is an exaggerated proliferative response to arteri al intimal injury. A successful means of limiting this hyperplastic re sponse would significantly improve patency rates of vascular reconstru ction. Angiotensin-converting enzyme (ACE) inhibitors decrease the pro liferation and synthetic function of vascular smooth muscle cells in v itro, which have been implicated in the production of intimal hyperpla sia. We performed a dose-response study of enalapril to assess the lev el at which maximal suppression of intimal hyperplasia occurs. Seventy male Sprague-Dawley rats weighing 250-300 grams underwent standardize d carotid artery balloon catheter endothelial denudation to induce int imal hyperplasia. Six groups of ten animals each were treated with dai ly intramuscular injections of one of the following doses of enalapril (mg/kg): 0.025, 0.050, 0.075, 0.100, 0.125, and 0.150. A control grou p (n = 10) was treated with saline. Injections were started two days b efore injury and continued for 4 weeks, at which time the injured arte ries were pressure-fixed in vivo and harvested. EVG-stained histologic cross-sections were measured by planimetry to determine the amount of intimal hyperplasia, which was calculated as the percentage of the ar terial lumen replaced by the lesion. Enalapril suppresses the developm ent of intimal hyperplasia in a dose-responsive manner in this model. No further suppression is achieved above a dose of 0.125 mg/kg.