- 作者: An-Sheng Lee; Wen-Pin Chen; Ming-Jai Su
- 作者服務機構: Institute of Pharmacology, College of Medicine,National Taiwan University, Taiwan, ROC
- 中文摘要: --
- 英文摘要: In Langendorff-perfused adult rat heart withconstant pressure at 80 mmHg, we found doxazosin, an a1 adrenoceptor blocker, at 10 uM prolonged PR intervaland induced occasional arrhythmia followed by completeinhibition of the sinus rhythm, whereas bunazosin, anothera1-blocker, at same concentration did not. The results ofvoltage-clamp study showed that, at the concentration of10 uM, doxazosin inhibited INa, I(Ca,L), Ito, and Iss withoutchanging Ik1 but bunazosin only inhibited I(Ca,L) about 30%.Doxazosin also caused markedly negative shift of the INainactivation curve. In current-clamp study, doxazosin prolongedaction potential duration in association with thedecreased action potential amplitude and upstroke velocity,whereas bunazosin did not. We hypothesize that doxazosininducedarrhythmia may result from the heterogeneous ordifferent level of I(Ca,L) blockade of AV nodal tissue. Inconclusion, the present study suggests that bunazosin issafer than doxazosin for long-term treatment in view ofelectrophysiological effect. However, the underlying mechanismof doxazosin induced nodal arrhythmia is still neededto be determined.
- 中文關鍵字: --
- 英文關鍵字: Alpha blockers; Electrophysiology; Langendorff-perfused heart; Arrhythmia