Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Toxicol In Vitro. 2013 Mar;27(2):932-8. doi: 10.1016/j.tiv.2013.01.004. Epub 2013 Jan 11.
Cigarette smoking is a leading cause of cardiovascular disease. The cardiovascular effects of smoking are probably multifactorial, including effects on platelets. Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent. The present study investigated in vitro effects of nicotine, its major metabolites, tobacco extracts and extract of tobacco-free snuff on human platelets. None of the metabolites cotinine, cotinine-N-oxide, nicotine-1'-N-oxide or trans-3'-hydroxycotinine (0.1-10 μM) affected platelet aggregation or P-selectin expression. Nicotine (10 μM) weakly increased platelet aggregation, whereas trans-3'-hydroxycotinine (0.1 μM) and nicotine-1'-N-oxide (1-10 μM) weakly inhibited adhesion to fibrinogen. To elucidate the influence of other tobacco compounds, we investigated the impact of moist tobacco and smoke extracts on platelet function. Filtered extracts of oral snuff, cigarette smoke and tobacco free snuff inhibited platelet adhesion concentration-dependently. The inhibitory effects of tobacco extracts on platelet adhesion were independent of nicotine content and the nitric-oxide-pathway and not mediated through a platelet-nicotine-receptor. Taken together, tobacco extracts inhibit platelet activation during short-term in vitro challenge. As only limited effects of nicotine and nicotine metabolites were seen, the tobacco-induced platelet inhibition are likely induced by other compounds present in tobacco and tobacco free snuff.
吸烟是心血管疾病的主要原因。吸烟对心血管的影响可能是多因素的，包括对血小板的影响。以前关于尼古丁和烟草对血小板功能影响的报告结果并不一致。本研究调查了尼古丁、其主要代谢物、烟草提取物和无烟草鼻烟提取物对人血小板的体外影响。代谢物可替宁、可替宁-N-氧化物、尼古丁-1'-N-氧化物或反式-3'-羟基可替宁（0.1-10 μM）均不影响血小板聚集或 P-选择素表达。尼古丁（10 μM）弱增加血小板聚集，而反式-3'-羟基可替宁（0.1 μM）和尼古丁-1'-N-氧化物（1-10 μM）弱抑制纤维蛋白原的黏附。为了阐明其他烟草化合物的影响，我们研究了湿润烟草和烟雾提取物对血小板功能的影响。口服鼻烟、香烟和无烟草鼻烟的过滤提取物浓度依赖性地抑制血小板黏附。烟草提取物对血小板黏附的抑制作用与尼古丁含量、一氧化氮途径无关，也不是通过血小板尼古丁受体介导的。综上所述，烟草提取物在体外短期刺激时抑制血小板活化。由于仅观察到尼古丁和尼古丁代谢物的有限作用，因此烟草引起的血小板抑制可能是由烟草和无烟草鼻烟中的其他化合物引起的。
