Comparison of the cardiac electrophysiological effects between doxazosin and bunazosin

In Langendorff-perfused adult rat heart with constant pressure at 80 mmHg, we found doxazosin, an α₁ adrenoceptor blocker, at 10 μM prolonged PR interval and induced occasional arrhythmia followed by complete inhibition of the sinus rhythm, whereas bunazosin, another α₁-blocker, at same concentration did not. The results of voltage-clamp study showed that, at the concentration of 10 μM, doxazosin inhibited I _Na, I _(Ca,L) , I _to, and Iss without changing I _k1 but bunazosin only inhibited I _(Ca,L) about 30%. Doxazosin also caused markedly negative shift of the I _Na inactivation curve. In current-clamp study, doxazosin prolonged action potential duration in association with the decreased action potential amplitude and upstroke velocity, whereas bunazosin did not. We hypothesize that doxazosin-induced arrhythmia may result from the heterogeneous or different level of I _(Ca,L) blockade of AV nodal tissue. In conclusion, the present study suggests that bunazosin is safer than doxazosin for long-term treatment in view of electrophysiological effect. However, the underlying mechanism of doxazosin induced nodal arrhythmia is still needed to be determined.