Regression of early events of atherosclerosis in hypercholesterolemic rabbits by prophylactic treatment with nitroderivative of acetyl salicylic acid

Abstract

The potential of a newly developed compound, nitro-aspirin (NO-aspirin, NCX-4016), on regression of early atherosclerotic events in hypercholesterolemic rabbit (HypR) was examined. Hypercholesterolemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days. During this induction period, HypRs were divided into two groups: one was given an oral single daily dose of 56 mg/kg/day NOaspirin in olive oil, whereas the other received olive oil alone and served as a control. A normal group of rabbits fed plain chow diet plus olive oil was also included. At the end of the 28 days, samples from blood, aorta, heart, and coronary arteries were separated for biochemical and histopathological examination. Tissues from HypR aorta and coronaries developed major changes that include formation of large intimal plaques, endothelial gaps with marked accumulation of foam cells. Highly significant increases in serum triglycerides and malondialdehyde and a decrease in reduced glutathione (GSH) in heart and aorta were also observed. Administration of NO-aspirin markedly improved aortic and coronary architecture to almost normal appearance. NO-aspirin also improved the antioxidant status in aorta and heart by increasing GSH levels and ameliorating malondialdehyde accumulation. These data support prophylactic use of NO-aspirin in regression of atherosclerosis. Drug Dev. Res. 53:237-243, 2001.