Niu X L, Liu L Y, Hu M L, Chen X
Department of Pharmacology, Hunan Medical University, Changsha, P.R. of China.
J Mol Cell Cardiol. 1995 Jan;27(1):531-9. doi: 10.1016/s0022-2828(08)80048-x.
In the present study oxidized low-density lipoproteins (ox-LDL) was prepared by a new simple method: oxidizing LDL by electrolysis-generated free radicals. In endothelium-intact norepinephrine(NE)-precontracted rabbit aortic rings, ox-LDL (2 mg protein/ml)-incubation for 30 min or 3 mM oleic acid for 10 min, significantly attenuated the acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) (both P < 0.01 v control). Such attenuated EDR were sustained after washout. The oleic acid-induced endothelial dysfunction was associated with concomitant reduction of cGMP level in aortic rings. Preincubation of aortic rings with 500 microM L-arginine or 100 u/ml superoxide dismutase for 10 min partly prevented the oleic acid-induced attenuation of EDR and reduction of cGMP, indicating that oleic acid may impair the L-arginine-nitric acid pathway and/or inactivate the nitric oxide. Both ox-LDL and oleic acid potentiated NE-induced aortic ring contraction (both P < 0.01 v control). Such potentiating effects were abolished by preincubation with 1 microM verapamil, indicating the possible involvement of calcium influx in vascular smooth muscle cells during the enhanced contraction. Gas-chromatographic analysis showed that oleic acid content is the highest among all free fatty acids in ox-LDL. In conclusion, we found that oleic acid possesses certain similar vascular effects as ox-LDL in inducing endothelial dysfunction and in enhancing NE-induced vasocontraction in rabbit aortic ring. We proposed that the vasoactive effects of ox-LDL may be resulted partly from the activation or release of active oleic acid molecule during oxidative modification of LDL.
在本研究中，氧化型低密度脂蛋白（ox-LDL）通过一种新的简单方法制备：用电解产生的自由基氧化低密度脂蛋白。在血管内皮完整且由去甲肾上腺素（NE）预收缩的兔主动脉环中，用ox-LDL（2 mg蛋白/ml）孵育30分钟或用3 mM油酸孵育10分钟，显著减弱了乙酰胆碱（ACh）诱导的内皮依赖性舒张（EDR）（与对照组相比，两者P < 0.01）。这种减弱的EDR在冲洗后仍持续存在。油酸诱导的内皮功能障碍与主动脉环中cGMP水平的同时降低有关。用500 microM L-精氨酸或100 u/ml超氧化物歧化酶预孵育主动脉环10分钟，部分预防了油酸诱导的EDR减弱和cGMP降低，表明油酸可能损害L-精氨酸-一氧化氮途径和/或使一氧化氮失活。ox-LDL和油酸均增强了NE诱导的主动脉环收缩（与对照组相比，两者P < 0.01）。用1 microM维拉帕米预孵育可消除这种增强作用，表明在增强的收缩过程中，钙内流可能参与了血管平滑肌细胞的活动。气相色谱分析表明，油酸含量在ox-LDL的所有游离脂肪酸中最高。总之，我们发现油酸在诱导兔主动脉环内皮功能障碍和增强NE诱导的血管收缩方面具有与ox-LDL某些相似的血管效应。我们提出，ox-LDL的血管活性作用可能部分源于LDL氧化修饰过程中活性油酸分子的激活或释放。
