Ishibashi Yutaka, Takahashi Nobuyuki, Tokumaru Atsushi, Karino Kenji, Sugamori Takashi, Sakane Takeshi, Yoshitomi Hiroyuki, Sato Hidetoshi, Oyake Nobuyuki, Murakami Yo, Shimada Toshio
Division of Cardiovascular Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
J Cardiovasc Pharmacol. 2008 Mar;51(3):311-6. doi: 10.1097/FJC.0b013e318163a95f.
Long-term administration of nicorandil has been shown to improve outcomes through cardioprotective effects in patients with coronary artery disease. To identify the mechanisms responsible for these effects, this study examined the impact of long-term nicorandil administration on endothelial function, systemic inflammatory markers, and oxidative stress in patients with cardiovascular risk factors. Fifty-three patients were assigned to receive either nicorandil therapy (15 mg/day; n = 26) (nicorandil group) or usual care (n = 27) (nonnicorandil group). All study participants underwent flow-mediated vasodilatation (FMD) of the brachial artery 1 month before treatment, just before treatment, and at 3, 6, and 12 months following treatment. At identical time points, serum levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and high-sensitivity C-reactive protein (hs-CRP) were collected. Compared with the nonnicorandil group, the nicorandil group demonstrated significantly increased FMD at 12 months, a finding not replicated for endothelium-independent vasodilatation with nitroglycerine. Analysis of biochemical markers revealed significantly reduced MAD-LDL levels in the nicorandil group at 12 months, as compared to slightly increased MAD-LDL levels in the nonnicorandil group. Significant reductions in hs-CRP levels were also noted at 6 and 12 months in the nicorandil group, while no change was found in the nonnicorandil group. Results demonstrated that long-term nicorandil therapy is associated with gradual improvements in endothelial function. Our findings also suggest that nicorandil treatment may result in cardiovascular protection through pleiotropic effects including reductions in oxidative injury and systemic inflammation.
长期服用尼可地尔已被证明可通过对冠心病患者的心脏保护作用改善预后。为确定这些作用的机制，本研究考察了长期服用尼可地尔对有心血管危险因素患者的内皮功能、全身炎症标志物和氧化应激的影响。53例患者被分配接受尼可地尔治疗（15毫克/天；n = 26）（尼可地尔组）或常规治疗（n = 27）（非尼可地尔组）。所有研究参与者在治疗前1个月、即将治疗时以及治疗后3、6和12个月接受肱动脉血流介导的血管舒张（FMD）检测。在相同时间点，收集丙二醛修饰的低密度脂蛋白（MDA-LDL）和高敏C反应蛋白（hs-CRP）的血清水平。与非尼可地尔组相比，尼可地尔组在12个月时FMD显著增加，而硝酸甘油介导的非内皮依赖性血管舒张未出现此结果。生化标志物分析显示，尼可地尔组在12个月时MAD-LDL水平显著降低，而非尼可地尔组MAD-LDL水平略有升高。尼可地尔组在6个月和12个月时hs-CRP水平也显著降低，而非尼可地尔组未发现变化。结果表明，长期尼可地尔治疗与内皮功能的逐渐改善相关。我们的研究结果还表明，尼可地尔治疗可能通过多效性作用实现心血管保护，包括减少氧化损伤和全身炎症。
