α-肾上腺素能受体拮抗剂对豚鼠心室肌的抗心律失常作用。

Antiarrhythmic effects of alpha-adrenoceptor antagonists in guinea pig ventricular myocardium.

作者信息

Hasegawa J, Hirai S, Saitoh M, Kotake H, Mashiba H

机构信息

Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.

出版信息

J Am Coll Cardiol. 1988 Dec;12(6):1590-8. doi: 10.1016/s0735-1097(88)80030-5.

DOI:10.1016/s0735-1097(88)80030-5

PMID:2903873

Abstract

Antiarrhythmic effects of alpha-adrenoceptor antagonists were assessed in the reserpinized guinea pig ventricular myocardium. Both bunazosin (1 to 3 x 10(-7) M), a new alpha 1-adrenoceptor antagonist, and yohimbine (1 to 3 x 10(-7) M), another adrenoceptor antagonist, suppressed the transient depolarization and triggered activity induced by a train of rapid stimuli in the solution containing low potassium ion (K+), high calcium ion (Ca2+) and strophanthidin (1 to 5 x 10(-7) M). Bunazosin (3 x 10(-6) M) abolished the facilitatory effect of hypoxia on beta-adrenoceptor mediated abnormal automaticity. To clarify the mechanisms underlying the antiarrhythmic properties of alpha-adrenoceptor antagonists, their electrophysiologic effects on the fast and slow action potentials were investigated. Alpha-adrenoceptor antagonists (bunazosin, yohimbine and phentolamine) suppressed the slow response in a dose-related manner. The voltage-dependent block and use-dependent block of the maximal rate of rise (Vmax) of action potentials by bunazosin (10(-5) to 10(-4) M) and yohimbine (10(-6) to 10(-5) M) were studied. The analysis of the onset and recovery kinetics from the use-dependent block of drugs showed that both bunazosin and yohimbine act as slow kinetic drugs. It is concluded that alpha-adrenoceptor antagonists seem to have an antiarrhythmic effect through the inhibition of fast sodium ion (Na+) and slow Ca2+ currents of the cell membrane independently of blockade of myocardial alpha-adrenoceptors.

摘要

在利血平化豚鼠心室肌中评估了α-肾上腺素能受体拮抗剂的抗心律失常作用。新型α1-肾上腺素能受体拮抗剂布那唑嗪（1至3×10⁻⁷M）和另一种肾上腺素能受体拮抗剂育亨宾（1至3×10⁻⁷M），均能抑制含低钾离子（K⁺）、高钙离子（Ca²⁺）和毒毛花苷（1至5×10⁻⁷M）溶液中一串快速刺激所诱发的瞬时去极化和触发活动。布那唑嗪（3×10⁻⁶M）消除了缺氧对β-肾上腺素能受体介导的异常自律性的促进作用。为阐明α-肾上腺素能受体拮抗剂抗心律失常特性的潜在机制，研究了它们对快、慢动作电位的电生理效应。α-肾上腺素能受体拮抗剂（布那唑嗪、育亨宾和酚妥拉明）以剂量相关方式抑制慢反应。研究了布那唑嗪（10⁻⁵至10⁻⁴M）和育亨宾（10⁻⁶至10⁻⁵M）对动作电位最大上升速率（Vmax）的电压依赖性阻滞和使用依赖性阻滞。对药物使用依赖性阻滞的起始和恢复动力学分析表明，布那唑嗪和育亨宾均为慢动力学药物。结论是，α-肾上腺素能受体拮抗剂似乎通过抑制细胞膜的快钠离子（Na⁺）和慢钙离子（Ca²⁺）电流而具有抗心律失常作用，这与心肌α-肾上腺素能受体的阻断无关。