Villablanca A C
Division of Cardiovascular Medicine, University of California, Davis, California 95616, USA.
J Appl Physiol (1985). 1998 Jun;84(6):2089-98. doi: 10.1152/jappl.1998.84.6.2089.
Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. Endothelial cell growth may be regulated by nicotine, yet operative mechanisms at the endothelial level are poorly understood. We studied the effects of nicotine (10(-14)-10(-4) M) on endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using cultures of bovine pulmonary artery endothelial cells. Assays were performed on cells incubated with nicotine in the presence and absence of hydroxyurea (an inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and platelet-derived growth factor and endothelial cell growth factor (PDGF and PDECGF, respectively). Nicotine significantly stimulated endothelial cell DNA synthesis and proliferation at concentrations lower than those obtained in blood after smoking (<10(-8) M). The stimulatory effects of nicotine were enhanced by serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist hexamethonium. The response to nicotine was bimodal because cytotoxicity was observed at higher concentrations (>10(-6) M). This study has implications for understanding cellular mechanisms of nicotine action. The results may be important in tumor angiogenesis, atherogenesis, and vascular dysfunction in smokers.
尼古丁是香烟烟雾的主要成分，据推测在动脉粥样硬化形成和恶性肿瘤发展中起重要作用。内皮细胞生长可能受尼古丁调节，但其在内皮水平的作用机制尚不清楚。我们利用牛肺动脉内皮细胞培养物研究了尼古丁（10⁻¹⁴ - 10⁻⁴ M）对内皮细胞DNA合成、DNA修复、增殖和细胞毒性的影响。在有和没有羟基脲（一种DNA合成抑制剂）、血清、人少血小板血浆以及血小板衍生生长因子和内皮细胞生长因子（分别为PDGF和PDECGF）存在的情况下，对用尼古丁孵育的细胞进行检测。尼古丁在低于吸烟后血液中浓度（<10⁻⁸ M）时显著刺激内皮细胞DNA合成和增殖。尼古丁的刺激作用在血清（0.5%）和PDECGF存在时增强，并被烟碱受体拮抗剂六甲铵阻断。对尼古丁的反应呈双峰，因为在较高浓度（>10⁻⁶ M）时观察到细胞毒性。本研究有助于理解尼古丁作用的细胞机制。这些结果对于理解吸烟者肿瘤血管生成、动脉粥样硬化形成和血管功能障碍可能具有重要意义。
