Odaka Ryosuke, Saito Taro, Seki Maika, Iinuma Akane, Takatsu Kousei, Hamaguchi Shogo, Namekata Iyuki, Tanaka Hikaru
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Biol Pharm Bull. 2024;47(12):2138-2142. doi: 10.1248/bpb.b24-00695.
The effect of a citrus-derived flavonoid, hesperetin, on the automaticity and contraction of isolated guinea pig myocardium was examined. Hesperetin inhibited the rate of ectopic action potential firing of the pulmonary vein myocardium; the slope of the diastolic depolarization was decreased with minimum change in the action potential waveform. The effect was dependent on the concentration; the EC value for firing rate was 56.2 ± 14.2 µM and that for the diastolic depolarization slope was 41.6 ± 13.4 µM. In the right atria, hesperetin had no effect on the beating rate at concentrations up to 30 µM, but showed a negative chronotropic effect at 100 µM. In the ventricular papillary muscles, hesperetin had no effect on the contractile force at concentrations up to 30 µM, but showed a slight positive inotropic effect at 100 µM. In isolated pulmonary vein cardiomyocytes, 30 µM hesperetin decreased the firing rate of spontaneous Ca transients. These results showed that hesperetin has a selective inhibitory action on the pulmonary vein automaticity with no inhibitory effect on the ventricular contractile force. Clarification of the mechanism of action of hesperetin as well as further exploration of flavonoids would provide clues for the development of pulmonary vein-selective therapeutic agents.
研究了一种源自柑橘的类黄酮橙皮素对豚鼠离体心肌自律性和收缩性的影响。橙皮素抑制肺静脉心肌异位动作电位的发放频率；舒张期去极化斜率降低，而动作电位波形变化最小。该作用取决于浓度；发放频率的EC值为56.2±14.2µM，舒张期去极化斜率的EC值为41.6±13.4µM。在右心房中，橙皮素在浓度高达30µM时对心率无影响，但在100µM时表现出负性变时作用。在心室乳头肌中，橙皮素在浓度高达30µM时对收缩力无影响，但在100µM时表现出轻微的正性变力作用。在离体肺静脉心肌细胞中，30µM橙皮素降低了自发钙瞬变的发放频率。这些结果表明，橙皮素对肺静脉自律性具有选择性抑制作用，而对心室收缩力无抑制作用。阐明橙皮素的作用机制以及对类黄酮的进一步探索将为开发肺静脉选择性治疗药物提供线索。
