Pharmacologic suppression of intimal hyperplasia: a dose-response suppression by enalapril.
Intimal hyperplasia is an exaggerated proliferative response to arterial intimal injury. A successful means of limiting this hyperplastic response would significantly improve patency rates of vascular reconstruction. Angiotensin-converting enzyme (ACE) inhibitors decrease the proliferation and synthetic function of vascular smooth muscle cells in vitro, which have been implicated in the production of intimal hyperplasia. We performed a dose-response study of enalapril to assess the level at which maximal suppression of intimal hyperplasia occurs. Seventy male Sprague-Dawley rats weighing 250-300 grams underwent standardized carotid artery balloon catheter endothelial denudation to induce intimal hyperplasia. Six groups of ten animals each were treated with daily 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 group (n = 10) was treated with saline. Injections were started two days before injury and continued for 4 weeks, at which time the injured arteries 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 arterial lumen replaced by the lesion. Enalapril suppresses the development of intimal hyperplasia in a dose-responsive manner in this model. No further suppression is achieved above a dose of 0.125 mg/kg.
Petrik
P V
PV
Section of Vascular Surgery, UCLA School of Medicine 90024, USA.
Law
M M
MM
Moore
W S
WS
Colburn
M D
MD
Quinones-Baldrich
W
W
Gelabert
H A
HA
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology* / Q000601:surgery; D002404:Catheterization / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D014654:Vascular Patency
D004656:Enalapril