• Kenji Iwata, Hiroki Iida, Mami Iida, Motoyasu Takenaka, Kumiko Tanabe, Naokazu Fukuoka, and Masayoshi Uchida.
• Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu Prefectural General Medical Center, Gifu-City, Gifu 501-1194, Japan.
• J Neurosurg Anesthesiol. 2013 Oct 1;25(4):392-8.

BackgroundOur 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 MethodsA 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 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.ResultsCerebral arterioles were dilated during topical ACh infusion. After smoking, 10 M ACh constricted cerebral arterioles (-7.7±1.8%). After smoking, in the nicorandil-pretreatment group, 10 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.ConclusionsAcute 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.

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