Author + information
- Received February 17, 1988
- Revision received July 20, 1988
- Accepted July 25, 1988
- Published online December 1, 1988.
- Junichi Hasegawa, MD, DMSc*,1,
- Shozo Hirai, MD1,
- Makoto Saitoh, MD1,
- Hiroshi Kotake, MD, DMSc1 and
- Hiroto Mashiba, MD, DMSc, FACC1
- ↵*Address for reprints:Junichi Hasegawa, MD, Department of Internal Medicine, Tottori University School of Medicine, 36-1 Nishimachi, Yonago 683, Japan.
Antiarrhythmic effects of alpha-adrenoceptor antagonists were assessed in the reserpinized guinea pig ventricular myocardium. Both bunazosin (1 to 3 x 10−7M), a new alpha1-adrenoceptor antagonist, and yohimbine (1 to 3 × 10−7M), 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 × 10−7M). Bunazosin (3 × 10−6M) 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 (10−5to 10−4M) and yohimbine (HT6 to 10−5M) 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 Jhe cell membrane independently of blockade of myocardial alpha-adrenoceptors.
- Received February 17, 1988.
- Revision received July 20, 1988.
- Accepted July 25, 1988.
- American College of Cardiology Foundation