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 H2O2-enhanced contractility of KCI-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 H2O2 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.
Heinle
H
H
Institute of Physiology, University of Tübingen, Germany.
Wülfroth
P
P
Quack
G
G
Lang
F
F
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002791:Cholesterol, Dietary / Q000494:pharmacology; D002951:Citrates / Q000097:blood; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000627:therapeutic use*; D011817:Rabbits
D000975:Antioxidants; D002791:Cholesterol, Dietary; D002951:Citrates; D008055:Lipids; D011725:Pyridines; D011189:Potassium Chloride; C100546:nicanartine; D006861:Hydrogen Peroxide