The unique action of nicorandil on cerebral circulation

The unique action of nicorandil on cerebral circulation Journal of Anesthesia (2018) 32:462 https://doi.org/10.1007/s00540-018-2499-3 LE T TER TO  THE   EDITOR 1,2 1 3 Hiroyuki Kinoshita  · Shinji Kawahito  · Kazumi Takaishi Received: 11 April 2018 / Accepted: 21 April 2018 / Published online: 4 May 2018 © Japanese Society of Anesthesiologists 2018 Keywords ATP-sensitive K channels · Cerebral artery · Nicorandil · Nitric oxide To the Editor: of rodents [3]. Second, whether nicorandil produces cerebral arterial dilation via KATPs is still unclear in animals. Indeed, Kotoda et al. [1] demonstrated that the intraperitoneal 1 mg/ the agent does not induce dilation of rat anterior cerebellar kg nicorandil without affecting systemic hemodynamics artery [4], and it causes relaxation via nitric oxide pathway, causes the increase in cerebral blood flow (CBF), which is but not KATP activation, in the canine basilar artery [5]. canceled by either an ATP-sensitive K channel (KATP) Therefore, the CBF enhancement by nicorandil is most likely antagonist glibenclamide or a non-selective nitric oxide to be mediated by mechanisms such as the increased cardiac synthase inhibitor N -nitro-l -arginine (l -NAME). They con- output resulting from systemic vasodilation other than that cluded that nicorandil produces the enhancement in CBF, originated from vasorelaxation in the brain. Collectively, we which is probably induced via both the nitric oxide pathway would like to await the additional study to verify the role of and KATPs [1]. We would like to add several discussions nicorandil in the cerebral circulation. regarding the conclusion. First, the systemic administration Funding The institutional funding supported this study. of l -NAME causes the reduction of CBF at the range of − 20 to − 40%, which is mediated by the nitric oxide synthase Compliance with ethical standards inhibition [2]. The CBF possibly remains unchanged within the baseline in the animals exposed to the systemic l -NAME, Conflict of interest Hiroyuki Kinoshita is a consult of IMI Co. Ltd, which results in the CBF reduction, in combination with the Koshigaya, Saitama, Japan. vasodilation induced by nicorandil. Therefore, there seems no evidence to conclude that nicorandil increases CBF via Financial support None. 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 References with glibenclamide on increased CBF by nicorandil. On the other hand, the activation of nitric oxide synthase might be 1. Kotoda M, Ishiyama T, Mitsui K, Hishiyama S, Matsukawa T. possible by the application of a KATP opener in the artery Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice. J Anesth. 2018;32:244–9. 2. Fouyas JP, Kelly PAT, Ritchie IM, Whittle IR. Cerebrovascular This comment refers to the article available at: https ://doi. responsiveness to N -nitro-l -arginine methylester in spontane- org/10.1007/s0054 0-018-2471-2. ously diabetic rats. Br J Pharmacol. 1996;118:243–8. 3. Kinoshita H, Iwahashi S, Kakutani T, Mizumoto K, Iranami * Hiroyuki Kinoshita H, Hatano Y. The role of endothelium-derived nitric oxide in hkinoshi@krc.biglobe.ne.jp relaxations to levcromakalim in the rat aorta. Jpn J Pharmacol. 1999;81:362–6. Department of Anesthesiology, Institute of Biomedical 4. McPherson GA, Stork AP. The resistance of some rat cerebral Sciences, Tokushima University Graduate School, arteries to the vasorelaxant effect of cromakalim and other K Tokushima, Japan channel openers. Br J Pharmacol. 1992;105:51 – 8. Department of Anesthesiology, IMS Fujimi General 5. Zhang H, Stockbridge N, Weir B, Vollrath B, Cook D. Vasodil- Hospital, Fujimi, Japan atation of canine cerebral arteries by nicorandil, pinacidil and lemakalim. Gen Pharmacol. 1992;23:197–201. Department of Dental Anesthesiology, Tokushima University Hospital, Tokushima, Japan Vol:.(1234567890) 1 3 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Anesthesia Springer Journals

The unique action of nicorandil on cerebral circulation

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Springer Journals
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Copyright © 2018 by Japanese Society of Anesthesiologists
Subject
Medicine & Public Health; Anesthesiology; Pain Medicine; Intensive / Critical Care Medicine; Emergency Medicine
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0913-8668
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1438-8359
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10.1007/s00540-018-2499-3
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Abstract

Journal of Anesthesia (2018) 32:462 https://doi.org/10.1007/s00540-018-2499-3 LE T TER TO  THE   EDITOR 1,2 1 3 Hiroyuki Kinoshita  · Shinji Kawahito  · Kazumi Takaishi Received: 11 April 2018 / Accepted: 21 April 2018 / Published online: 4 May 2018 © Japanese Society of Anesthesiologists 2018 Keywords ATP-sensitive K channels · Cerebral artery · Nicorandil · Nitric oxide To the Editor: of rodents [3]. Second, whether nicorandil produces cerebral arterial dilation via KATPs is still unclear in animals. Indeed, Kotoda et al. [1] demonstrated that the intraperitoneal 1 mg/ the agent does not induce dilation of rat anterior cerebellar kg nicorandil without affecting systemic hemodynamics artery [4], and it causes relaxation via nitric oxide pathway, causes the increase in cerebral blood flow (CBF), which is but not KATP activation, in the canine basilar artery [5]. canceled by either an ATP-sensitive K channel (KATP) Therefore, the CBF enhancement by nicorandil is most likely antagonist glibenclamide or a non-selective nitric oxide to be mediated by mechanisms such as the increased cardiac synthase inhibitor N -nitro-l -arginine (l -NAME). They con- output resulting from systemic vasodilation other than that cluded that nicorandil produces the enhancement in CBF, originated from vasorelaxation in the brain. Collectively, we which is probably induced via both the nitric oxide pathway would like to await the additional study to verify the role of and KATPs [1]. We would like to add several discussions nicorandil in the cerebral circulation. regarding the conclusion. First, the systemic administration Funding The institutional funding supported this study. of l -NAME causes the reduction of CBF at the range of − 20 to − 40%, which is mediated by the nitric oxide synthase Compliance with ethical standards inhibition [2]. The CBF possibly remains unchanged within the baseline in the animals exposed to the systemic l -NAME, Conflict of interest Hiroyuki Kinoshita is a consult of IMI Co. Ltd, which results in the CBF reduction, in combination with the Koshigaya, Saitama, Japan. vasodilation induced by nicorandil. Therefore, there seems no evidence to conclude that nicorandil increases CBF via Financial support None. 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 References with glibenclamide on increased CBF by nicorandil. On the other hand, the activation of nitric oxide synthase might be 1. Kotoda M, Ishiyama T, Mitsui K, Hishiyama S, Matsukawa T. possible by the application of a KATP opener in the artery Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice. J Anesth. 2018;32:244–9. 2. Fouyas JP, Kelly PAT, Ritchie IM, Whittle IR. Cerebrovascular This comment refers to the article available at: https ://doi. responsiveness to N -nitro-l -arginine methylester in spontane- org/10.1007/s0054 0-018-2471-2. ously diabetic rats. Br J Pharmacol. 1996;118:243–8. 3. Kinoshita H, Iwahashi S, Kakutani T, Mizumoto K, Iranami * Hiroyuki Kinoshita H, Hatano Y. The role of endothelium-derived nitric oxide in hkinoshi@krc.biglobe.ne.jp relaxations to levcromakalim in the rat aorta. Jpn J Pharmacol. 1999;81:362–6. Department of Anesthesiology, Institute of Biomedical 4. McPherson GA, Stork AP. The resistance of some rat cerebral Sciences, Tokushima University Graduate School, arteries to the vasorelaxant effect of cromakalim and other K Tokushima, Japan channel openers. Br J Pharmacol. 1992;105:51 – 8. Department of Anesthesiology, IMS Fujimi General 5. Zhang H, Stockbridge N, Weir B, Vollrath B, Cook D. Vasodil- Hospital, Fujimi, Japan atation of canine cerebral arteries by nicorandil, pinacidil and lemakalim. Gen Pharmacol. 1992;23:197–201. Department of Dental Anesthesiology, Tokushima University Hospital, Tokushima, Japan Vol:.(1234567890) 1 3

Journal

Journal of AnesthesiaSpringer Journals

Published: May 4, 2018

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