Nicorandil prevents epinephrine-induced arrhythmias in halothane-anesthetized rats by nitric oxide-dependent mechanism |
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Authors: | Yusuke Kawai Yukio Hayashi Isao Ito Takahiko Kamibayashi Koji Takada Kiyokazu Kagawa Atsushi Yamatodani Takashi Mashimo |
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Institution: | 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 |
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Abstract: | 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. |
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