Role of cardiac α 1 -adrenoreceptors for the torsadogenic action of I Kr blocker nifekalant in the anesthetized atrioventricular block rabbit.

Autor: Kawakami S; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan., Kambayashi R; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan; Department of Pharmacology, Faculty of Medicine, Toho University, Ota-ku, Tokyo, 143-8540, Japan., Takada K; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan., Aimoto M; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan., Nagasawa Y; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan., Takahara A; Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba 274-8510, Japan. Electronic address: akirat@phar.toho-u.ac.jp.
Jazyk: angličtina
Zdroj: Journal of pharmacological sciences [J Pharmacol Sci] 2022 Oct; Vol. 150 (2), pp. 67-73. Date of Electronic Publication: 2022 Jul 31.
DOI: 10.1016/j.jphs.2022.07.003
Abstrakt: We analyzed role of cardiac α 1 -adrenoreceptors for the torsadogenic action of I Kr blocker nifekalant in isoflurane-anesthetized atrioventricular block rabbits. Bradycardia was induced by atrioventricular node ablation, and the ventricle was electrically driven at a constant rate of 60 beats/min throughout the experiments to prevent rate-dependent modification by the I Kr blocker in ventricular repolarization phase. Nifekalant (3 mg/kg per 10 min, n = 5) prolonged the duration of monophasic action potential (MAP 90 ) by +178 ± 43 ms, increased the short-term variability of repolarization (STV) to 4.2 ± 1.2 ms, and induced torsade de pointes (TdP) in 1 animal. In the presence of methoxamine (n = 5), nifekalant prolonged the MAP 90 by +328 ± 32 ms, increased the STV to 8.0 ± 1.0 ms, and induced TdP in 2 animals. In the presence of prazosin and methoxamine (n = 5), nifekalant prolonged the MAP 90 by +267 ± 22 ms, increased the STV to 9.2 ± 3.6 ms, and induced no TdP. These results suggest that cardiac α 1 -adrenoreceptor activation by methoxamine essentially sensitizes the rabbit heart to nifekalant-induced QT interval prolongation, leading to the onset of TdP.
Competing Interests: Declaration of competing interest The authors state no conflict of interest.
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Databáze: MEDLINE
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