Hutchison S J, Reitz M S, Sudhir K, Sievers R E, Zhu B Q, Sun Y P, Chou T M, Deedwania P C, Chatterjee K, Glantz S A, Parmley W W
Vascular Research Laboratory, University of California, San Francisco, USA.
Hypertension. 1997 May;29(5):1186-91. doi: 10.1161/01.hyp.29.5.1186.
Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.
我们的目标是确定在不存在高胆固醇血症的情况下，环境烟草烟雾是否会导致内皮功能障碍，以及补充L-精氨酸是否可以预防这种影响。接触环境烟草烟雾与冠状动脉疾病事件和死亡率增加有关。我们之前已经证明，环境烟草烟雾会导致饮食诱导的高胆固醇血症和动脉粥样硬化的兔子出现内皮功能障碍和动脉粥样硬化，而长期饮食补充L-精氨酸可预防这种情况。在32只喂食正常饮食的兔子中，采用2×2设计研究了补充L-精氨酸（2.25%溶液随意饮用）和环境烟草烟雾（在吸烟室暴露10周）的影响。在预先用去氧肾上腺素预收缩的主动脉环中评估乙酰胆碱、钙离子载体A23187和硝酸甘油诱导的血管舒张。通过色谱法测量内皮L-精氨酸水平。长期补充L-精氨酸可提高血清（P<.001）和内皮（P=.003）L-精氨酸水平。环境烟草烟雾降低了内皮依赖性乙酰胆碱诱导的舒张，而L-精氨酸可阻断这种不良影响（P=.04）。环境烟草烟雾倾向于增加去氧肾上腺素诱导的收缩（P=.06）。环境烟草烟雾和L-精氨酸均未影响A23187诱导的舒张或非内皮依赖性硝酸甘油诱导的舒张。在不存在饮食诱导的高胆固醇血症和动脉粥样硬化的情况下，环境烟草烟雾继发的内皮功能障碍可能会发生。长期饮食补充一氧化氮供体如L-精氨酸可抵消正常胆固醇血症兔子中与环境烟草烟雾相关的内皮功能障碍，可能是通过一氧化氮途径的底物加载实现的。
