Biology Department, Faculty of Arts and Sciences, Zonguldak Karaelmas University, ncivez/Zonguldak, Turkey.
J Cardiovasc Pharmacol Ther. 2010 Dec;15(4):403-11. doi: 10.1177/1074248410372925. Epub 2010 Aug 5.
this study was performed to assess the effect of selective sarcolemmal adenosine triphosphate (ATP)-sensitive K(+) channel (K(ATP)) inhibition and the mitochondrial K(ATP) channel activation on ischemia and reperfusion (I/R)-induced arrhythmias in different gender of rats. We compared the effect of a selective sarcolemmal K(ATP) channel blocker HMR 1098, a selective mitochondrial K(ATP) channel opener diazoxide, a nonselective K(ATP) channel opener pinacidil, and the combination of pinacidil with HMR 1098 on the incidence and duration of ventricular arrhythmias in 2 groups: anesthetized males (n = 31) and females (n = 31).
ischemia and reperfusion was produced by occluding the left main coronary artery of Sprague-Dowley rats for 6 minutes followed by re-opening of the artery for 6 minutes.
the arrhythmia score and the duration of arrhythmias were significantly reduced by HMR 1098, diazoxide, and pinacidil in male rats. The combination of the pinacidil with HMR 1098 did not change the antiarrhythmic effect of pinacidil. The duration of arrhythmas was shorter in females than that in the corresponding males. Drug treatments were not effective in decreasing arrhythmias in female groups to the same extent as in the male group. However, the mitochondrial K( ATP) channel activation that is provided by the combination of pinacidil with HMR 1098 significantly decreased the total length of arrhythmias in females.
results of the current study indicate that both mitochondrial K(ATP) channel activation and sarcolemmal K(ATP) channel inhibition exert antiarrhythmic action in male rats. The antiarrhythmic effect of pinacidil is not depend on the sarcolemmal K(ATP) channel opening. These results also indicate that K(ATP) channel modulators show no discernable effect in female rats due to the already low incidence of arrhythmias in females.
本研究旨在评估选择性肌浆网三磷酸腺苷（ATP）敏感钾（KATP）通道（KATP）抑制和线粒体 KATP 通道激活对不同性别大鼠缺血再灌注（I/R）诱导心律失常的影响。我们比较了选择性肌浆网 KATP 通道阻滞剂 HMR 1098、选择性线粒体 KATP 通道开放剂二氮嗪、非选择性 KATP 通道开放剂吡那地尔以及吡那地尔与 HMR 1098 联合应用对 2 组大鼠（麻醉雄性 n = 31 和雌性 n = 31）室性心律失常发生率和持续时间的影响。
通过阻断 Sprague-Dowley 大鼠左冠状动脉主干 6 分钟，然后再开放动脉 6 分钟，产生缺血再灌注。
HMR 1098、二氮嗪和吡那地尔显著降低雄性大鼠的心律失常评分和心律失常持续时间。吡那地尔与 HMR 1098 联合应用并未改变吡那地尔的抗心律失常作用。与相应的雄性大鼠相比，雌性大鼠的心律失常持续时间较短。药物治疗并不能使雌性大鼠的心律失常减少到与雄性大鼠相同的程度。然而，吡那地尔与 HMR 1098 联合应用激活线粒体 KATP 通道，显著减少了雌性大鼠心律失常的总长度。
本研究结果表明，线粒体 KATP 通道激活和肌浆网 KATP 通道抑制在雄性大鼠中均具有抗心律失常作用。吡那地尔的抗心律失常作用不依赖于肌浆网 KATP 通道的开放。这些结果还表明，由于雌性大鼠心律失常的发生率已经较低，KATP 通道调节剂在雌性大鼠中没有明显作用。
