Grieve D J, Avella M A, Botham K M, Elliott J
Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, UK.
Eur J Pharmacol. 1998 May 8;348(2-3):181-90. doi: 10.1016/s0014-2999(98)00142-3.
The effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta were studied in vitro. Chylomicrons and chylomicron remnants were prepared in vivo. Aortic rings were incubated with the lipoproteins for 45 min before the vessels were constricted with phenylephrine and concentration relaxation response curves constructed to carbachol, ATP, A23187 and S-nitroso-N-acetylpenicillamine. Maximum % relaxations to carbachol were significantly reduced by both chylomicrons and chylomicron remnants but responses to ATP and S-nitroso-N-acetylpenicillamine were unaffected. In addition, chylomicrons significantly inhibited A23187-induced relaxation, causing an increase in the EC50 value. Chylomicron remnants cause selective inhibition of carbachol-induced relaxation suggesting an action at the receptor or G protein-coupled component of the receptor-mediated activation of the L-arginine-nitric oxide pathway. Chylomicrons appear to be less selective in their inhibition of the endothelium-dependent relaxation. This study demonstrates that lipoprotein particles of dietary origin may cause endothelial cell dysfunction.
在体外研究了乳糜微粒和乳糜微粒残粒对大鼠主动脉内皮依赖性舒张的影响。乳糜微粒和乳糜微粒残粒在体内制备。在用去氧肾上腺素收缩血管之前,将主动脉环与脂蛋白孵育45分钟,然后构建对卡巴胆碱、ATP、A23187和S-亚硝基-N-乙酰青霉胺的浓度舒张反应曲线。乳糜微粒和乳糜微粒残粒均显著降低了对卡巴胆碱的最大舒张百分比,但对ATP和S-亚硝基-N-乙酰青霉胺的反应未受影响。此外,乳糜微粒显著抑制A23187诱导的舒张,导致半数有效浓度(EC50)值增加。乳糜微粒残粒选择性抑制卡巴胆碱诱导的舒张,提示其作用于受体或受体介导的L-精氨酸-一氧化氮途径激活的G蛋白偶联成分。乳糜微粒对内皮依赖性舒张的抑制作用似乎选择性较低。本研究表明,饮食来源的脂蛋白颗粒可能导致内皮细胞功能障碍。