Grieve D J, Avella M A, Elliott J, Botham K M
Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, UK.
Atherosclerosis. 1998 Aug;139(2):273-81. doi: 10.1016/s0021-9150(98)00078-1.
A system for the perfusion of the isolated rat aorta which allowed the study of both the uptake of chylomicron remnants by the artery wall and their effects on endothelial function was developed. Perfusion for 2 h with 125I-labelled native or oxidised (by treatment with copper sulphate) chylomicron remnants showed that small amounts became associated with the artery wall (0.111 +/- 0.034 and 0.216 +/- 0.082 ng protein/mg tissue, respectively). Tests on endothelial function were carried out in vessel rings prepared after perfusion of the aortas in the presence or absence of chylomicron remnants for 2 h. After perfusion of the vessels with oxidised chylomicron remnants, the maximum response to phenylephrine (PE) was significantly increased (from 0.34 +/- 0.06 to 0.51 +/- 0.04 g/mg tissue; P < 0.05), while the maximum % relaxation to carbachol (CCh) was significantly decreased (from 91.6 +/- 2.4 to 71.5 +/- 7.2; P < 0.05) and the response to S-nitroso-N-acetylpenicillimine (SNAP) was unaffected. Perfusion with native chylomicron remnants showed a tendency to induce similar effects, although the changes observed did not reach statistical significance. As the lipoproteins were not present in the solution bathing the vessel rings during these tests, these effects can be attributed to perfusion of the aortas with chylomicron remnants, despite only small quantities being associated with the artery wall. The results suggest that oxidised chylomicron remnants influence vascular endothelial function by interfering with the L-arginine-nitric oxide (NO) pathway. The observed potentiation of contraction to PE may be due to inhibition of the basal release of NO or to the release of contractile factors. These findings support a role for dietary lipoproteins in the modulation of endothelial cell function which occurs in the pathogenesis of atherosclerosis.
开发了一种用于灌注离体大鼠主动脉的系统，该系统能够研究动脉壁对乳糜微粒残粒的摄取及其对内皮功能的影响。用125I标记的天然或氧化（用硫酸铜处理）乳糜微粒残粒灌注2小时，结果表明少量残粒与动脉壁结合（分别为0.111±0.034和0.216±0.082 ng蛋白/mg组织）。在有或没有乳糜微粒残粒存在的情况下，对主动脉进行2小时灌注后制备血管环，进行内皮功能测试。用氧化乳糜微粒残粒灌注血管后，对去氧肾上腺素（PE）的最大反应显著增加（从0.34±0.06增加到0.51±0.04 g/mg组织；P<0.05），而对卡巴胆碱（CCh）的最大舒张百分比显著降低（从91.6±2.4降低到71.5±7.2；P<0.05），对S-亚硝基-N-乙酰青霉胺（SNAP）的反应未受影响。用天然乳糜微粒残粒灌注显示出诱导类似效应的趋势，尽管观察到的变化未达到统计学显著性。由于在这些测试期间，血管环浸泡的溶液中不存在脂蛋白，因此这些效应可归因于用乳糜微粒残粒灌注主动脉，尽管只有少量与动脉壁结合。结果表明，氧化乳糜微粒残粒通过干扰L-精氨酸-一氧化氮（NO）途径影响血管内皮功能。观察到的对PE收缩增强可能是由于抑制了NO的基础释放或收缩因子的释放。这些发现支持饮食脂蛋白在动脉粥样硬化发病机制中发生的内皮细胞功能调节中的作用。
