Nicorandil prevents epinephrine-induced arrhythmias in halothane-anesthetized rats by nitric oxide-dependent mechanism.
The effect of opening ATP-sensitive K(+) channels on the genesis of arrhythmias is still controversial. We investigated the effect of nicorandil, an ATP-sensitive K(+) channel opener, on the genesis of halothane-epinephrine arrhythmias in rats. We also clarified the involvement of nitric oxide in the effect of nicorandil. Furthermore, we studied the effect of levcromakalim, another ATP-sensitive K(+) channel opener, for comparison. Nicorandil and levcromakalim significantly increased the arrhythmogenic thresholds of epinephrine in a dose-dependent manner. On the other hand, nitroprusside, a potent vasodilator (5.0 micro g/kg per min), did not exert antiarrhythmic action significantly. Both glibenclamide (non-specific ATP-sensitive K(+) channel blocker) and 5-hydroxydecanoate (mitochondrial ATP-sensitive K(+) channel blocker) inhibited the antiarrhythmic action of nicorandil. Although pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, did not modulate the genesis of halothane-epinephrine arrhythmias in the absence of nicorandil, it completely abolished the antiarrhythmic action of nicorandil, but not the effect of levcromakalim. We concluded that nicorandil dose-dependently inhibited halothane-epinephrine arrhythmias through mitochondrial ATP-sensitive K(+) channels and nitric oxide is required for the antiarrhythmic effect of nicorandil.
Kawai
Yusuke
Y
Department of Anesthesiology (D-7), Osaka University Faculty of Medicine, 2-2, Yamada-oka, Suita Osaka, 565-0871, Japan. ykawai@anes.med.osaka-u.ac.jp
Hayashi
Yukio
Y
Ito
Isao
I
Kamibayashi
Takahiko
T
Takada
Koji
K
Kagawa
Kiyokazu
K
Yamatodani
Atsushi
A
Mashimo
Takashi
T
D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020108:Nicorandil / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D020108:Nicorandil; D009569:Nitric Oxide; D006221:Halothane; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine