title: Dexamethasone and enalapril suppress intimal hyperplasia individually but have no synergistic effect.
abstract: Vascular injury is associated with complex interactions that lead to development of intimal hyperplasia (IH). We have demonstrated previously that the corticosteroid dexamethasone and the ACE-inhibitor enalapril are effective in suppressing the development of IH. We hypothesize that due to distinctly different pharmacologic mechanisms of action, a synergistic effect would be expected if these agents were given in combination. Forty New Zealand White rabbits underwent balloon catheter denudation 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 mg/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 measured as a ratio of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (IH/IEL). Mean values for IH/IEL are 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 groups demonstrated significant suppression of IH compared to the control 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-agent therapy in suppressing the development of IH, suggesting that maximal suppression is obtained with single-agent treatment or that these agents affect IH through a common pathway.
authors.affiliation: Section of Vascular Surgery, UCLA School of Medicine, Los Angeles, California 90024, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Petrik
authors.forename: M M
authors.initials: MM
authors.lastname: Law
authors.forename: W S
authors.initials: WS
authors.lastname: Moore
authors.forename: M D
authors.initials: MD
authors.lastname: Colburn
authors.forename: W
authors.initials: W
authors.lastname: Quiñones-Baldrich
authors.forename: H A
authors.initials: HA
authors.lastname: Gelabert
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D004656:Enalapril / Q000494:pharmacology*; D005352:Fibromuscular Dysplasia / Q000473:pathology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007273:Injections, Intramuscular; D008297:Male; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D005938:Glucocorticoids; D004656:Enalapril; D003907:Dexamethasone