Chujo M, Mori H, Tanaka E, Nakazawa H, Okino H
Department of Physiology, School of Medicine, Tokai University, Kanagawa, Japan.
Cardiovasc Res. 1994 Jun;28(6):917-22. doi: 10.1093/cvr/28.6.917.
The aim was to investigate whether nicorandil suppresses the rise in coronary vascular resistance that occurs during stimulation of the sympathetic nerve supply to the heart and, if so, what are the mechanisms of action.
The effects of nicorandil on coronary vascular resistance during ventrolateral cardiac nerve stimulation and on the reactivity of the coronary vasculature to intracoronary infusion of noradrenaline or neuropeptide Y (NPY) were examined under beta receptor blockade. The effects of nicorandil on the overflow of noradrenaline and NPY during ansae subclaviae stimulation were compared with those in a control group and in a group treated with glyceryl trinitrate and N omega-nitro-L-arginine (L-NNA) under both alpha and beta receptor blockade with vagotomy.
Intracoronary infusion of nicorandil decreased coronary vascular resistance prior to cardiac nerve stimulation, and during stimulation it suppressed the percentage increase in resistance from the prestimulation value. Nicorandil suppressed the reactivity of the coronary vasculature to exogenous noradrenaline and NPY. Intra-atrial infusion of nicorandil significantly reduced the overflow of NPY but not of noradrenaline during stimulation of the ansae subclaviae at 20 Hz. This suppressive effect was not observed in the glyceryl trinitrate + L-NNA group.
Nicorandil reduces sympathetic coronary vasoconstriction by decreasing the reactivity of the vasculature to sympathetic neurotransmitters and by suppressing NPY overflow during cardiac sympathetic nerve stimulation. The suppressive action on NPY overflow is thought to be due to the opening of ATP sensitive potassium channels in the sympathetic nerve endings rather than to a glyceryl trinitrate-like action of nicorandil.
研究尼可地尔是否能抑制心脏交感神经刺激时发生的冠状动脉血管阻力升高，若能抑制，其作用机制是什么。
在β受体阻断情况下，检测尼可地尔对心脏外侧神经刺激时冠状动脉血管阻力的影响，以及对冠状动脉血管对冠状动脉内注入去甲肾上腺素或神经肽Y（NPY）反应性的影响。将尼可地尔对锁骨下神经刺激时去甲肾上腺素和NPY溢出的影响，与在α和β受体阻断并切断迷走神经的情况下，对照组以及用硝酸甘油和Nω-硝基-L-精氨酸（L-NNA）处理组的影响进行比较。
冠状动脉内注入尼可地尔在心脏神经刺激前降低了冠状动脉血管阻力，且在刺激过程中抑制了阻力相对于刺激前值的百分比增加。尼可地尔抑制了冠状动脉血管对外源性去甲肾上腺素和NPY的反应性。心房内注入尼可地尔在以20Hz刺激锁骨下神经时，显著降低了NPY的溢出，但未降低去甲肾上腺素的溢出。在硝酸甘油+L-NNA组未观察到这种抑制作用。
尼可地尔通过降低血管对交感神经递质的反应性以及抑制心脏交感神经刺激时的NPY溢出，来减轻交感神经介导的冠状动脉血管收缩。对NPY溢出的抑制作用被认为是由于交感神经末梢ATP敏感性钾通道开放，而非尼可地尔类似硝酸甘油的作用。
