Antiarrhythmic effects of alpha-adrenoceptor antagonists in guinea pig ventricular myocardium.
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.
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D011799:Quinazolines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013327:Strophanthidin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D011799:Quinazolines; D011943:Receptors, Adrenergic, beta; D013327:Strophanthidin; C018176:bunazosin; D002118:Calcium