Both nicotine and vascular endothelial growth factor (VEGF) have been proposed to play an important role in the development and progression of atherosclerosis. In vitro and ex vivo studies have demonstrated that nicotine significantly stimulates VEGF expression in several cell types. This study examined the effects and the mechanisms of nicotine on the expression of VEGF in a rabbit model of balloon-injured aortas. Forty-eight male New Zealand white rabbits were randomly divided into sham, control, nicotine, and nicotine plus hexamethonium (nicotine-hex) groups. Balloon catheter denuding injury iliac artery was performed in control, nicotine, and nicotine-hex animals fed with a high-cholesterol diet beginning 2 weeks before operation. Twenty-four hours after surgery, nicotine (0.05 microg/kg) or nicotine (0.05 microg/kg) and hexamethonium (6 mg/kg) was administered daily by intramuscular injection for 3 weeks in nicotine and nicotine-hex groups, respectively. Sham and control rabbits received an identical volume of phosphate-buffered saline injection, but without nicotine or hexamethonium. VEGF protein expression and intimal cell proliferation in balloon-injured aortas were determined by enzyme-link immunosorbent assay, immunohistochemistry, and Western blot analysis. Six rabbits died during the experiment. The remaining 42 rabbits were included in the study. VEGF protein expression in nicotine group was significantly higher than that in control group (P < 0.01). VEGF positive staining was seen in vascular endothelial cells, vascular smooth muscle cells, and infiltrative inflammatory cells. The number of the proliferative cells in intima was also significantly higher in nicotine group than in control group (P < 0.01). Hexamethonium, a nonselective antagonist of nicotinic acetylcholine receptors (nAChRs), significantly inhibited nicotine-induced VEGF protein expression (P < 0.01). The present study shows that intramuscular administration of nicotine markedly potentiates the expression of VEGF protein in balloon-injured rabbit aortas, which appears to be mediated through nAChRs.

中文翻译：

---

尼古丁增强了球囊损伤兔主动脉中血管内皮生长因子的表达。

尼古丁和血管内皮生长因子（VEGF）都被认为在动脉粥样硬化的发生和发展中起重要作用。体外和离体研究表明，尼古丁可在多种细胞类型中显着刺激VEGF表达。这项研究检查了尼古丁对家兔球囊损伤主动脉模型VEGF表达的影响及其机制。48只雄性新西兰大白兔随机分为假，对照组，尼古丁和尼古丁加六甲铵（尼古丁-十六进制）组。对照，尼古丁和尼古丁-六角动物在手术前2周开始喂饲高胆固醇饮食，对患者的performed总动脉进行球囊导管剥蚀性损伤。手术后二十四小时，服用尼古丁（0.05 microg / kg）或尼古丁（0。尼古丁组和尼古丁-十六进制组分别通过肌内注射每天给药05 microg / kg和六甲铵（6 mg / kg）。假手术和对照组的兔子接受相同体积的磷酸盐缓冲液注射，但是没有尼古丁或六甲铵。通过酶联免疫吸附法，免疫组化和Western blot分析确定球囊损伤主动脉中VEGF蛋白的表达和内膜细胞增殖。实验期间有六只兔子死亡。其余42只兔子被纳入研究。尼古丁组VEGF蛋白表达显着高于对照组（P <0.01）。在血管内皮细胞，血管平滑肌细胞和浸润性炎症细胞中可见VEGF阳性染色。尼古丁组内膜中增殖细胞的数量也显着高于对照组（P <0.01）。六甲铵是烟碱乙酰胆碱受体（nAChRs）的非选择性拮抗剂，可显着抑制烟碱诱导的VEGF蛋白表达（P <0.01）。本研究表明，尼古丁的肌内给药显着增强了气球蛋白损伤的兔主动脉中VEGF蛋白的表达，这似乎是通过nAChRs介导的。