Effects of the new antioxidant nicanartine in an experimental model of atherosclerosis

Transmural direct current (DC) stimulation of rabbit carotid arteries for 4 weeks was used for induction of atherosclerotic lesions. Ten animals received nicanartine (5-(3,5-di-tert-butyl)-4-hydroxyphenyl-1-(3-pyridyl)-2-oxapentane, CAS 150443-71-3, Mrz 3/124) which reveals antioxidative as well as cholesterol-lowering properties supplemented to the diet containing 0.1%) cholesterol. Controls were 10 rabbits without drug. Effects on plaque growth were determined by comparing the thickness of the DC induced intimal lesions in both groups. Furthermore, using non-stimulated segments of carotid arteries vasoprotecting effects were characterized by measuring H 2 O 2 -enhanced contractility of KCl-induced contraction as well as relaxation caused by acetylcholine induced liberation of endothelial derived relaxing factors. The results show decreased plaque growth during DC stimulation, diminished effectivity of H 2 O 2 on contractility and improved endothelial function in the drug treated group. Since plasma cholesterol was only marginally increased under these feeding conditions, the plaque-reducing effect is most probably due to the antioxidative properties of nicanartine. Similar effects on neointima formation were also shown for other antioxidants.