ANTIARRHYTHMIC EFFECTS OF ALPHA-ADRENOCEPTOR ANTAGONISTS IN GUINEA-PIG VENTRICULAR MYOCARDIUM

[摘要] Antiarrhythmic effects of alpha-adrenoceptor antagonists were assessed in the reserpinized guinea pig ventricular myocardium. Both bunazosin (1 to 3 .times. 10-7 M), a new alpha1-adrenoceptor antagonist, and yohimbine (1 to 3 .times. 10-7 M), another adrenoceptor antagonist, suppressed the transient depolarization and triggered activity induced by a train of rapid stimuli in the solution containig low potassium ion (K+), high calcium ion (Ca2+) and strophanthidin (1 to 5 .times. 10-7 M). Bunazosin (3 .times. 10-6 M) abolished the facilitatory effect of hypoia 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 (.ovrhdot.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 antagonist 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.

[发布日期] 1988-12-01