Hutchison S J, Sievers R E, Zhu B Q, Sun Y P, Stewart D J, Parmley W W, Chatterjee K
Division of CardiologyUniversity of California, San Francisco, San Francisco, CA 94143-0124, USA.
Chest. 2001 Dec;120(6):2004-12. doi: 10.1378/chest.120.6.2004.
To determine whether secondhand smoke (SHS) induces pulmonary artery endothelial dysfunction, and whether dietary L-arginine supplementation is preventive.
SHS causes coronary and peripheral arterial endothelial dysfunction.
The effects of L-arginine supplementation (2.25% solution) and SHS (10 weeks) on pulmonary vascular reactivity were examined in 32 rabbits fed a normal diet. Endothelium-dependent relaxation of precontracted pulmonary artery segments was studied using acetylcholine and calcium ionophore. Endothelium-independent relaxation was studied using nitroglycerin. Endothelial and serum L-arginine levels were measured by chromatography. In eight SHS-exposed and in eight control rats, pulmonary artery nitric oxide synthase (NOS) activity and arginase activity were studied using the titrated arginine to citrulline conversion assay.
SHS reduced maximal acetylcholine-induced (p = 0.04) and calcium ionophore-induced (p = 0.02) relaxation. L-Arginine increased maximal acetylcholine-induced (p = 0.047) vasodilation. SHS and L-arginine did not influence nitroglycerin-induced relaxation. SHS reduced endothelial L-arginine (p = 0.04) but not serum L-arginine. L-Arginine supplementation increased endothelial (p = 0.007) and serum L-arginine (p < 0.0005). Endothelium-dependent relaxation induced by acetylcholine and calcium ionophore varied directly with endothelial (r = 0.67, r = 0.67) and serum L-arginine (r = 0.43, r = 0.45), respectively. SHS reduced constitutive NOS activity (p = 0.03).
SHS reduces pulmonary artery endothelium-dependent relaxation by decreasing NOS activity and possibly by decreasing endothelial arginine content. L-Arginine supplementation increases serum and endothelial L-arginine stores and prevents SHS-induced endothelial dysfunction. L-Arginine may offset the deleterious effect of SHS on pulmonary arteries by substrate loading of the nitric oxide pathway.
确定二手烟（SHS）是否会诱发肺动脉内皮功能障碍，以及补充膳食L-精氨酸是否具有预防作用。
二手烟会导致冠状动脉和外周动脉内皮功能障碍。
在32只喂食正常饮食的兔子中，研究了补充L-精氨酸（2.25%溶液）和二手烟暴露（10周）对肺血管反应性的影响。使用乙酰胆碱和钙离子载体研究预收缩肺动脉段的内皮依赖性舒张。使用硝酸甘油研究非内皮依赖性舒张。通过色谱法测量内皮和血清L-精氨酸水平。在8只暴露于二手烟的大鼠和8只对照大鼠中，使用滴定的精氨酸向瓜氨酸转化测定法研究肺动脉一氧化氮合酶（NOS）活性和精氨酸酶活性。
二手烟降低了乙酰胆碱诱导的最大舒张（p = 0.04）和钙离子载体诱导的最大舒张（p = 0.02）。L-精氨酸增加了乙酰胆碱诱导的最大血管舒张（p = 0.047）。二手烟和L-精氨酸不影响硝酸甘油诱导的舒张。二手烟降低了内皮L-精氨酸（p = 0.04），但不影响血清L-精氨酸。补充L-精氨酸增加了内皮L-精氨酸（p = 0.007）和血清L-精氨酸（p < 0.0005）。乙酰胆碱和钙离子载体诱导的内皮依赖性舒张分别与内皮L-精氨酸（r = 0.67，r = 0.67）和血清L-精氨酸（r = 0.43，r = 0.45）直接相关。二手烟降低了组成型NOS活性（p = 0.03）。
二手烟通过降低NOS活性并可能通过降低内皮精氨酸含量来降低肺动脉内皮依赖性舒张。补充L-精氨酸可增加血清和内皮L-精氨酸储备，并预防二手烟诱导的内皮功能障碍。L-精氨酸可能通过一氧化氮途径的底物加载来抵消二手烟对肺动脉的有害影响。
