Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran.
J Surg Res. 2011 Jul;169(1):9-15. doi: 10.1016/j.jss.2009.10.025. Epub 2009 Nov 10.
Our previous study showed that pretreatment with noradrenaline via opening of the mitochondrial ATP-sensitive potassium channel protects myocardium against ischemia/reperfusion injuries. We have hypothesized that production of nitric oxide (NO) and generation of reactive oxygen species (ROS) are involved in noradrenaline-induced cardioprotection in rat heart.
All anesthetized rats underwent 25 min of regional ischemia followed by 120 min of reperfusion. Animals were randomized to receive one of the following treatment: saline, noradrenaline (2 μg/kg, i.v.), noradrenaline plus prazosin (an α(1)-adrenoceptor blocker, 0.5mg/kg, i.v.), noradrenaline plus L-NAME (a nonspecific NOS inhibitor, 10mg/kg, i.v.), noradrenaline plus tempol (a membrane-permeable radical scavenger, 30 mg/kg, i.v.), Prazosin alone, only L-NAME and tempol alone.
Infarct size (% of risk area) was reduced from 49.6 ± 2.4 in saline-control group to 18.2 ± 1.5 in noradrenaline preconditioned group. Administration of prazosin, L-NAME, or tempol prior to noradrenaline injection abolished the observed cardioprotection of noradrenaline (45.5 ± 3, 41.7 ± 4.5 and 38.7 ± 5.4, respectively) and restored infarct size to saline-control rats' level. Incidences and severity of ventricular arrhythmia during ischemia and early reperfusion significantly decreased in noradrenaline preconditioned group compared with saline-control group. This cardioprotective effect of noradrenaline against ventricular arrhythmia was abrogated by administration of prazosin, L-NAME, or tempol.
Cardioprotection effect of the α(1)-adrenoceptor stimulation by noradrenaline was inhibited by L-NAME or tempol in anesthetized rat heart.
我们之前的研究表明，通过开放线粒体三磷酸腺苷敏感性钾通道预处理去甲肾上腺素可保护心肌免受缺血/再灌注损伤。我们假设一氧化氮（NO）的产生和活性氧（ROS）的产生参与了去甲肾上腺素诱导的大鼠心脏保护作用。
所有麻醉大鼠均接受 25 分钟的区域缺血，然后进行 120 分钟的再灌注。动物被随机分为以下治疗组之一：生理盐水、去甲肾上腺素（2μg/kg，静脉注射）、去甲肾上腺素加哌唑嗪（α（1）-肾上腺素受体阻滞剂，0.5mg/kg，静脉注射）、去甲肾上腺素加 L-NAME（非特异性一氧化氮合酶抑制剂，10mg/kg，静脉注射）、去甲肾上腺素加 Tempo（膜通透性自由基清除剂，30mg/kg，静脉注射）、哌唑嗪单独使用、仅 L-NAME 和 Tempo 单独使用。
与生理盐水对照组（49.6±2.4）相比，去甲肾上腺素预处理组的梗死面积（风险区域的百分比）减少至 18.2±1.5。在去甲肾上腺素注射前给予哌唑嗪、L-NAME 或 Tempo 会消除去甲肾上腺素观察到的心脏保护作用（分别为 45.5±3、41.7±4.5 和 38.7±5.4），并使梗死面积恢复到生理盐水对照组大鼠的水平。与生理盐水对照组相比，去甲肾上腺素预处理组在缺血和再灌注早期的室性心律失常发生率和严重程度显著降低。去甲肾上腺素对室性心律失常的这种心脏保护作用被哌唑嗪、L-NAME 或 Tempo 阻断。
在麻醉大鼠心脏中，去甲肾上腺素对α（1）-肾上腺素受体的刺激作用被 L-NAME 或 Tempo 抑制。
