Heinle H, Wülfroth P, Quack G, Lang F
Institute of Physiology, University of Tübingen, Germany.
Arzneimittelforschung. 1996 Oct;46(10):956-9.
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.
采用兔颈动脉壁全层直流电刺激4周来诱导动脉粥样硬化病变。10只动物在含0.1%胆固醇的饮食中添加了尼卡兰汀（5-(3,5-二叔丁基)-4-羟基苯基-1-(3-吡啶基)-2-氧杂戊烷，CAS 150443-71-3，Mrz 3/124），该药物具有抗氧化和降胆固醇特性。对照组为10只未用药的兔子。通过比较两组直流电诱导的内膜病变厚度来确定对斑块生长的影响。此外，利用颈动脉未受刺激的节段，通过测量过氧化氢增强氯化钾诱导收缩的收缩力以及乙酰胆碱诱导内皮源性舒张因子释放所引起的舒张，来表征血管保护作用。结果显示，在直流电刺激期间，药物治疗组的斑块生长减少，过氧化氢对收缩力的作用减弱，内皮功能改善。由于在这些喂养条件下血浆胆固醇仅略有升高，斑块减少效应很可能归因于尼卡兰汀的抗氧化特性。其他抗氧化剂对新生内膜形成也显示出类似作用。
