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Erschienen in: Journal of Anesthesia 2/2018

05.03.2018 | Original Article

Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice

verfasst von: Masakazu Kotoda, Tadahiko Ishiyama, Kazuha Mitsui, Sohei Hishiyama, Takashi Matsukawa

Erschienen in: Journal of Anesthesia | Ausgabe 2/2018

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Abstract

Purpose

Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (KATP) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method.

Methods

Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only. CBF was measured using a transcranial Doppler flowmeter. NG-nitro-l-arginine methyl ester and glibenclamide were used to elucidate the underlying mechanisms.

Results

A single-bolus injection of 1 mg/kg of nicorandil increased the CBF (11.6 ± 3.6 vs. 0.5 ± 0.7%, p < 0.001) without affecting the heart rate and blood pressure. On the contrary, 5 and 10 mg/kg of nicorandil significantly decreased the cerebral blood flow by decreasing the mean blood pressure below the cerebral autoregulation range. The positive effect of 1 mg/kg of nicorandil on the cerebral blood flow was inhibited by co-administration of either NG-nitro-l-arginine methyl ester or glibenclamide.

Conclusions

A clinical dose of nicorandil increases CBF without affecting systemic hemodynamics. The positive effect of nicorandil on CBF is most likely caused via both the nitric oxide pathway and KATP channel opening.
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Metadaten
Titel
Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice
verfasst von
Masakazu Kotoda
Tadahiko Ishiyama
Kazuha Mitsui
Sohei Hishiyama
Takashi Matsukawa
Publikationsdatum
05.03.2018
Verlag
Springer Japan
Erschienen in
Journal of Anesthesia / Ausgabe 2/2018
Print ISSN: 0913-8668
Elektronische ISSN: 1438-8359
DOI
https://doi.org/10.1007/s00540-018-2471-2

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