The unique action of nicorandil on cerebral circulation
The unique action of nicorandil on cerebral circulation
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尼可地尔对脑循环的独特作用
DOI：
10.1007/s00540-018-2499-3
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发表时间：
2018
影响因子：
2.8
通讯作者：
Takaishi Kazumi
中科院分区：
文献类型：
--
作者：
Kinoshita Hiroyuki;Kawahito Shinji;Takaishi Kazumi
Kotoda等人[1]研究表明，腹膜内1 mg/kg尼可地尔在不影响全身血流动力学的情况下导致脑血流量（CBF）增加，这可被ATP敏感性K+通道（KATP）拮抗剂格列本脲或非选择性一氧化氮合酶抑制剂NG-硝基-L-精氨酸（l-NAME）抵消。他们得出结论，尼可地尔可增强CBF，这可能通过一氧化氮途径和KATP诱导[1]。我们想就结论补充几点讨论。首先，全身给予l-NAME会导致CBF减少-20至40%，这是由一氧化氮合酶抑制介导的[2]。在暴露于全身性l-NAME的动物中，CBF可能在基线范围内保持不变，这导致CBF降低，并伴有尼可地尔诱导的血管舒张。因此，似乎没有证据表明尼可地尔通过提高一氧化氮水平增加CBF，自Kotoda et al. [1]未检查l-NAME单独给药对初始CBF的影响以及一氧化氮抑制剂与格列本脲联合给药对尼可地尔引起的CBF增加的影响。另一方面，在啮齿动物动脉中应用KATP开放剂可能会激活一氧化氮合酶[3]。其次，尼可地尔是否通过KATP在动物中产生脑动脉扩张尚不清楚。事实上，该药物不会诱导大鼠小脑前动脉扩张[4]，并且在犬基底动脉中通过一氧化氮途径而不是KATP激活引起舒张[5]。因此，尼可地尔的CBF增强最有可能是由机制介导的，例如全身血管舒张导致的心输出量增加，而不是源于脑血管舒张的机制。总之，我们希望等待额外的研究来验证尼可地尔在脑循环中的作用。
Kotoda et al.[1] demonstrated that the intraperitoneal 1 mg/kg nicorandil without affecting systemic hemodynamics causes the increase in cerebral blood flow (CBF), which is canceled by either an ATP-sensitive K+ channel (KATP) antagonist glibenclamide or a non-selective nitric oxide synthase inhibitor NG-nitro-l-arginine (l-NAME). They concluded that nicorandil produces the enhancement in CBF, which is probably induced via both the nitric oxide pathway and KATPs [1]. We would like to add several discussions regarding the conclusion. First, the systemic administration of l-NAME causes the reduction of CBF at the range of− 20 to− 40%, which is mediated by the nitric oxide synthase inhibition [2]. The CBF possibly remains unchanged within the baseline in the animals exposed to the systemic l-NAME, which results in the CBF reduction, in combination with the vasodilation induced by nicorandil. Therefore, there seems no evidence to conclude that nicorandil increases CBF via the enhanced levels of nitric oxide since Kotoda et al.[1] did not examine the effect of l-NAME alone on the naïve CBF and that of the nitric oxide inhibitor in combination with glibenclamide on increased CBF by nicorandil. On the other hand, the activation of nitric oxide synthase might be possible by the application of a KATP opener in the artery of rodents [3]. Second, whether nicorandil produces cerebral arterial dilation via KATPs is still unclear in animals. Indeed, the agent does not induce dilation of rat anterior cerebellar artery [4], and it causes relaxation via nitric oxide pathway, but not KATP activation, in the canine basilar artery [5]. Therefore, the CBF enhancement by nicorandil is most likely to be mediated by mechanisms such as the increased cardiac output resulting from systemic vasodilation other than that originated from vasorelaxation in the brain. Collectively, we would like to await the additional study to verify the role of nicorandil in the cerebral circulation.
尼可地尔、吡那地尔和莱马卡林对犬脑动脉的血管舒张作用。
DOI：
10.1016/0306-3623(92)90009-9
发表时间：
1992
期刊：
General pharmacology
影响因子：
--
作者：
H. Zhang;N. Stockbridge;B. Weir;B. Vollrath;D. Cook
通讯作者：
D. Cook
自发性糖尿病大鼠脑血管对 NG-硝基-L-精氨酸甲酯的反应
影响因子：
7.3
作者：
I. Fouyas;P. Kelly;I. Ritchie;I. Whittle
通讯作者：
I. Whittle