Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice
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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.
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.
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.
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.
KeywordsCerebral blood flow KATP channel Neuroprotection Nicorandil Nitric oxide
This work was supported by the Japan Society for Promotion of Science (JSPS KAKENHI Grant number 17K11044).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
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