Fasudil prevents KATP channel-induced improvement in postischemic functional recovery.
Fasudil prevents KATP channel-induced improvement in postischemic functional recovery.
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Fasudil 可防止 KATP 通道诱导的缺血后功能恢复改善。
DOI：
10.1152/ajpheart.00611.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Pike,MartinM
中科院分区：
文献类型：
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作者：
Nishizawa,Kenya;Wolkowicz,PaulE;Yamagishi,Tadashi;Guo,Ling-Ling;Pike,MartinM
尽管ATP依赖性钾（KATP）通道的激活极大地改善了缺血后心肌的恢复，但KATP通道诱导的心脏保护的最终效应机制仍不清楚。RhoA是一种GTdR，其调节已知与KATP通道心脏保护有关的多种细胞过程。我们的目标是确定一个关键的rhoA效应，rho激酶（ROCK）的活性，是否需要KATP通道诱导的心脏保护。将4组大鼠心脏进行36 min零流量缺血和44 min再灌注，连续测量机械功能和31 P NMR高能磷酸盐数据：1）未处理，2）吡那地尔（10 μM）激活ATP通道，3）法舒地尔（15 μM）抑制ROCK，4）法舒地尔和吡那地尔。吡那地尔显著改善了缺血后的机械恢复[未治疗组和吡那地尔组左心室舒张压（LVDP）分别为39 ± 16和108 ± 4 mmHg]。法舒地尔不影响再灌注LVDP（41 ± 13 mmHg），但完全阻断了吡那地尔治疗（54 ± 15 mmHg）时机械恢复的显著改善。还观察到缺血后能量恢复的显著衰减。这些数据支持ROCK活性在KATP通道诱导的心脏保护中起作用的假设。
Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATPchannel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATPchannel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for KATPchannel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and31P NMR high-energy phosphate data:1) untreated,2) pinacidil (10 μM) to activate KATPchannels,3) fasudil (15 μM) to inhibit ROCK, and4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATPchannel-induced cardioprotection.