KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated preconditioning by glibenclamide.
KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated preconditioning by glibenclamide.
复制标题
大鼠心脏中的 KATP 通道：格列本脲阻断缺血和乙酰胆碱介导的预处理。
DOI：
10.1152/ajpheart.1996.271.1.h23
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Kukreja,RC
中科院分区：
文献类型：
--
作者：
Qian,YZ;Levasseur,JE;Yoshida,K;Kukreja,RC
本研究的目的是检查 ATP 敏感 K+ (KATP) 通道的开放是否在大鼠心脏缺血预适应 (PC) 中发挥重要作用。第二个目标是测试乙酰胆碱 (ACh) 在模拟 PC 中的作用，并测试它是否可以被 KATP 拮抗剂阻断。格列本脲是 KATP 通道的特异性拮抗剂，在 PC 前 60 和 30 分钟给予两次剂量，每次 0.3 mg/kg。使用以下方案对六组大鼠进行缺血和再灌注 (I/R)：1) 对照 (I/R)，30 分钟缺血，然后再灌注 90 分钟（n = 6 只大鼠）； 2) 在 I/R 前 10 分钟给予预处理心脏 5 分钟缺血（n = 9 只大鼠）； 3）PC前60和30分钟格列本脲（0.3 mg/kg）治疗（n = 13只大鼠）； 4) I/R前格列本脲治疗（n = 15只大鼠）； 5)以0.15ml/min的速率输注ACh 5分钟(18微克/ml)，然后在I/R之前平衡10分钟，n = 13只大鼠； 6) 在 ACh 输注之前进行格列本脲治疗，然后进行 I/R（n = 11 只大鼠）。预处理将梗塞面积（以危险面积百分比表示）从对照的 42.0 +/- 4.4% 减少到 8.7 +/- 6%（平均值 +/- SE，P < 0.05）。格列本脲阻断了 PC 赋予的保护作用（39.1 +/- 4.5%，P < 0.05），但对对照非预处理心脏没有显着影响。用 ACh 输注代替 PC 还可将梗塞面积减少至 25.0 +/- 5.63%（与对照相比，P < 0.05），这再次被格列本脲阻断（44.2 +/- 5.0%，P < 0.05）。数据表明，KATP 通道的开放对于缺血和乙酰胆碱介导的预处理在大鼠心脏中也很重要。
The objective of this study was to examine if the opening of ATP-sensitive K+ (KATP) channels play an important role in ischemic preconditioning (PC) in the rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60 and 30 min before PC. Six groups of rats were subjected to ischemia and reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment 60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n = 15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min followed by equilibration for 10 min before I/R, n = 13 rats; and 6) glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats). Preconditioning reduced the infarcted area (expressed as percent area at risk) from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05). Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05) without having a significant effect on control nonpreconditioned hearts. ACh infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05 compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%, P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh-mediated preconditioning is also important in the rat heart.