Variations of Endothelium Antioxidant Enzymes and Nitrite/Nitrate Levels in Collar-Induced Atherosclerosis of Rabbits
Endothelial Derived Relaxing Factor (EDRF) has been identified as Nitric Oxide (NO) and this endothelial product relaxes vascular smooth muscle and prevents platelet adhesion to the endothelial surface through a cyclic 3−5− guanosine monophosphate-mediated mechanism. There are some evidence linking excess vascular oxidative stress to the impairment of EDRF action associated with hypercholesterolemia. Recently, it’s shown that arteries derived from cholesterol fed rabbits produce excess Superoxide and the administration of Superoxide dismutase (SOD) to atherosclerotic rabbits improves EDRF action. Although it has been shown that excess vascular oxidative stress contributes to impaired EDRF action in experimental hypercholesterolemia and atherosclerosis, there are no data in literature related to antioxidant enzymes in intima bearing vessels predisposing to atherosclerosis. Since intimai thickening is an essential prerequisite for the development of atherosclerosis, the aims of our preliminary study was to investigate the role of antioxidant activity and NO levels in collar-induced intimai thickening by measuring the antioxidant enzymes (SOD and catalase). The intimai thickening was induced by a silicone collar placed around the left carotid artery for 2 weeks and the sham-operated, right carotid artery served as control. After 14 days the rabbits were anesthetized, blood samples were taken and both carotid arteries were dissected. Together with nitrite/nitrate level, SOD and catalase activities in erythrocytes and dissected collared and control carotid artery tissues were measured. While the catalase activity and nitrate level in intima bearing collared carotid artery segments were higher than the control arteries (0.996 ± 0.25 vs. 2.104 ± 0.31 U/mg protein and 302 ± 8.17 vs. 431 ± 78.94 umol/mg tissue respectively), the SOD activity in collared arteries were significantly lower (14.06 ± 2.09 vs. 10.22 ± 0.88 U/mg protein). Since EDRF is readily inactivated by Superoxide and the action of EDRF is dependent upon intact endothelium SOD activity. The data demonstrated that EDRF inactivation may occur by depending on oxidative stress and lowering SOD activity in collared-induced intimai thickening without hypercholesterolemia and LDL oxidation.