Nicorandil protects pial arterioles from endothelial dysfunction induced by smoking in rat.
Nicorandil protects pial arterioles from endothelial dysfunction induced by smoking in rat.
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尼可地尔保护大鼠软脑膜小动脉免受吸烟引起的内皮功能障碍。
DOI：
10.1097/ana.0b013e318295aa93
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发表时间：
2013
影响因子：
3.7
通讯作者：
Uchida M
中科院分区：
文献类型：
--
作者：
Iwata K;Iida H;Iida M;Takenaka M;Tanabe K;Fukuoka N;Uchida M
背景：我们的目的是研究尼可地尔，这是用于心绞痛的预防和治疗，对急性吸烟引起的内皮功能障碍的影响，并阐明其潜在的mechanism.Materials和方法：一个封闭的颅窗制备用于测量软膜血管直径的变化在Sprague-Dawley大鼠。吸烟前检测小动脉对内皮依赖性血管舒张剂乙酰胆碱（ACh）的反应。尼可地尔静脉（200 μg/kg推注，然后60 μg/kg/min连续输注; n= 6）或生理盐水（对照; n= 6）预处理后，在吸烟1分钟前和吸烟1分钟后1小时重新检查软膜血管扩张剂对局部10− 5 M ACh输注的反应。此后，在尼可地尔输注前20分钟输注格列本脲或N-ω-硝基-L-精氨酸甲酯（L-NAME）。在格列本脲（n= 6）或L-NAME; n= 6预处理组，软膜血管扩张反应局部乙酰胆碱进行了检查之前和之后吸烟。结果：局部注射乙酰胆碱可使脑小动脉扩张。吸烟后，10− 5 M ACh使脑小动脉收缩（− 7.7±1.8%）。吸烟后，在尼可地尔预处理组中，10 - 5 M ACh使脑软膜小动脉扩张10.5± 3.0%。当给予尼可地尔输注前，格列本脲，但不是L-NAME，取消尼可地尔对吸烟引起的软脑膜血管内皮功能障碍的预防作用：急性吸烟导致内皮依赖性软脑膜血管舒张功能障碍，尼可地尔防止吸烟的影响。这种保护作用的机制可能主要取决于腺苷三磷酸敏感的钾通道激活。
Background:Our aims are to investigate the effect of nicorandil, which is used for angina prevention and treatment, on the endothelial dysfunction induced by acute smoking and to clarify the underlying mechanism.Materials and Methods:A closed cranial window preparation was used to measure changes in pial vessel diameters in Sprague-Dawley rats. The responses of arterioles were examined to an endothelium-dependent vasodilator acetylcholine (ACh) before smoking. After intravenous nicorandil (200 μg/kg bolus infusion and then 60 μg/kg/min continuous infusion; n= 6) or saline (control; n= 6) pretreatment, the pial vasodilator response to topical 10− 5 M ACh infusion was reexamined both before and 1 hour after 1-minute cigarette smoking. Thereafter, either glibenclamide or N-ω-nitro-L-arginine methyl ester (L-NAME) was infused 20 minutes before nicorandil infusion. In the glibenclamide (n= 6) or L-NAME; n= 6 pretreatment group, the pial vasodilator response to topical ACh was examined before and after smoking. Percentage changes in pial vessel diameters were used for the statistical analysis.Results:Cerebral arterioles were dilated during topical ACh infusion. After smoking, 10− 5 M ACh constricted cerebral arterioles (− 7.7±1.8%). After smoking, in the nicorandil-pretreatment group, 10− 5 M ACh dilated cerebral pial arterioles by 10.5±3.0%. When given before nicorandil infusion, glibenclamide, but not L-NAME, abolished the preventive effects of nicorandil against smoking-induced endothelial dysfunction in pial vessels.Conclusions:Acute cigarette smoking causes dysfunction of endothelium-dependent pial vasodilatation, and nicorandil prevents this effect of smoking. The mechanism underlying this protective effect may depend mainly on adenosine triphosphate–sensitive potassium-channel activation.