Goulter Andrew B, Avella Michael A, Elliott Jonathan, Botham Kathleen M
Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College St, London NW1 0TU, UK.
Clin Sci (Lond). 2002 Nov;103(5):451-60. doi: 10.1042/cs1030451.
The influence of native and oxidized chylomicron-remnant-like particles (CMR-LPs) on endothelium-dependent relaxation in pig coronary arteries was studied. Artificial lipid particles of a size and lipid composition resembling chylomicron remnants and containing pig apolipoprotein E were used to investigate the effects of chylomicron remnants on the relaxation of isolated segments of pig coronary arteries in response to three endothelium dilators: 5-hydroxytryptamine (5-HT), bradykinin and the calcium ionophore A23187. CMR-LPs caused significant inhibition of the maximum relaxation response of the vessels to 5-HT, but not that to bradykinin or A23187 ( P <0.05). In contrast, CMR-LPs that had been oxidized by incubation with 10 microM CuSO(4) (oxidized CMR-LPs) were found to significantly reduce maximal relaxation to bradykinin by 13% ( P <0.05) and to reduce the sensitivity of the tissue to A23187 by 1.7-fold ( P <0.05). In experiments in which either the L-arginine/nitric oxide (NO) pathway or the endothelium-derived hyperpolarizing factor (EDHF) pathway was selectively inhibited, leaving the other intact, the inhibitory effect of oxidized CMR-LPs was observed only in vessels in which the -arginine/NO-mediated pathway was operative. Furthermore, the oxidized particles had no inhibitory effect on the relaxation of the vessel segments to the non-endothelium-dependent agonists S -nitro- N -acetylpenicillamine, 5'-( N -ethylcarboxamido)adenosine or pinacidil. These results demonstrate that CMR-LPs inhibit vascular relaxation in pig coronary arteries by an endothelium-dependent mechanism involving the L-arginine/NO pathway, but not the EDHF pathway, and provide evidence in support of a role for chylomicron remnants in the endothelial dysfunction associated with hypercholesterolaemia and atherogenesis.
研究了天然和氧化的乳糜微粒残粒样颗粒（CMR-LPs）对猪冠状动脉内皮依赖性舒张的影响。使用大小和脂质组成类似于乳糜微粒残粒且含有猪载脂蛋白E的人工脂质颗粒，来研究乳糜微粒残粒对猪冠状动脉离体节段对三种内皮舒张剂的舒张反应的影响，这三种舒张剂分别是：5-羟色胺（5-HT）、缓激肽和钙离子载体A23187。CMR-LPs显著抑制血管对5-HT的最大舒张反应，但对缓激肽或A23187的最大舒张反应无抑制作用（P<0.05）。相反，经与10微摩尔硫酸铜孵育氧化的CMR-LPs（氧化的CMR-LPs）被发现可使对缓激肽的最大舒张反应显著降低13%（P<0.05），并使组织对A23187的敏感性降低1.7倍（P<0.05）。在选择性抑制L-精氨酸/一氧化氮（NO）途径或内皮衍生超极化因子（EDHF）途径而使另一条途径保持完整的实验中，仅在L-精氨酸/NO介导途径起作用的血管中观察到氧化的CMR-LPs的抑制作用。此外，氧化颗粒对血管节段对非内皮依赖性激动剂S-硝基-N-乙酰青霉胺、5'-（N-乙基羧酰胺）腺苷或吡那地尔的舒张无抑制作用。这些结果表明，CMR-LPs通过涉及L-精氨酸/NO途径而非EDHF途径的内皮依赖性机制抑制猪冠状动脉的血管舒张，并为乳糜微粒残粒在与高胆固醇血症和动脉粥样硬化相关的内皮功能障碍中的作用提供了证据支持。
