Journal of Anesthesia (2018) 32:462
LETTER TO THE EDITOR
The unique action of nicorandil on cerebral circulation
· 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:
Kotoda et al.  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
antagonist glibenclamide or a non-selective nitric oxide
synthase inhibitor N
-NAME). They con-
cluded that nicorandil produces the enhancement in CBF,
which is probably induced via both the nitric oxide pathway
and KATPs . We would like to add several discussions
regarding the conclusion. First, the systemic administration
-NAME causes the reduction of CBF at the range of − 20
to − 40%, which is mediated by the nitric oxide synthase
inhibition . The CBF possibly remains unchanged within
the baseline in the animals exposed to the systemic
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. 
did not examine the eﬀect of
-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 . 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 , and it causes relaxation via nitric oxide pathway,
but not KATP activation, in the canine basilar artery .
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.
Funding The institutional funding supported this study.
Compliance with ethical standards
Conflict of interest Hiroyuki Kinoshita is a consult of IMI Co. Ltd,
Koshigaya, Saitama, Japan.
Financial support None.
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Nicorandil increased the cerebral blood ﬂow via nitric oxide
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This comment refers to the article available at: https ://doi.
* Hiroyuki Kinoshita
Department of Anesthesiology, Institute of Biomedical
Sciences, Tokushima University Graduate School,
Department of Anesthesiology, IMS Fujimi General
Hospital, Fujimi, Japan
Department of Dental Anesthesiology, Tokushima University
Hospital, Tokushima, Japan