Ockaili R A, Bhargava P, Kukreja R C
Division of Cardiology, Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2406-11. doi: 10.1152/ajpheart.2001.280.5.H2406.
We investigated the cardioprotective effect of 3-nitropropionic acid (3-NPA), an inhibitior of mitochondrial succinate dehydrogenase, and we wanted to show whether this protection is mediated by of opening mitochondrial ATP-sensitive potassium (K(ATP)) channels. Adult rabbits were treated with either 3-NPA (3 mg/kg iv) or saline (n = 6 rabbits/group). After 30 min (for early phase) or 24 h (for late phase) of the treatment, the animals were subjected to 30 min of ischemia and 3 h of reperfusion (ischemia-reperfusion). 5-Hydroxydecanoate (5-HD, 5 mg/kg iv),the mitochondrial K(ATP) channel blocker, was administered 10 min before ischemia-reperfusion in the saline- and 3-NPA-treated rabbits. 3-NPA caused a decrease in the infarct size from 27.8 +/- 4.2% in the saline group to 16.5 +/- 1.0% in the 3-NPA-treated rabbits during early phase and from 30.4 +/- 4.2% in the saline group to 17.6 +/- 1.05 in the 3-NPA group during delayed phase (P < 0.05, % of risk area). The anti-infarct effect of 3-NPA was blocked by 5-HD as shown by an increase in infarct size to 33 +/- 2.7% (early phase) and 31 +/- 2.4% (delayed phase) (P < 0.05 vs. 3-NPA groups). 5-HD had no proischemic effect in control animals. Also, 3-NPA had no effect on systemic hemodynamics. We conclude that 3-NPA induces long-lasting anti-ischemic effects via opening of mitochondrial K(ATP) channels.
我们研究了线粒体琥珀酸脱氢酶抑制剂3-硝基丙酸（3-NPA）的心脏保护作用，并且想要证实这种保护作用是否通过开放线粒体ATP敏感性钾（K(ATP)）通道介导。成年兔分别用3-NPA（3mg/kg静脉注射）或生理盐水处理（每组n = 6只兔）。处理30分钟（早期）或24小时（晚期）后，使动物经历30分钟缺血和3小时再灌注（缺血-再灌注）。在生理盐水处理组和3-NPA处理组的兔缺血-再灌注前10分钟给予线粒体K(ATP)通道阻滞剂5-羟基癸酸（5-HD，5mg/kg静脉注射）。在早期，3-NPA使梗死面积从生理盐水组的27.8±4.2%降至3-NPA处理组的16.5±1.0%，在延迟期，从生理盐水组的30.4±4.2%降至3-NPA组的17.6±1.05%（P<0.05，危险区域百分比）。5-HD阻断了3-NPA的抗梗死作用，梗死面积增加至33±2.7%（早期）和31±2.4%（延迟期）（与3-NPA组相比，P<0.05）。5-HD在对照动物中没有促缺血作用。此外，3-NPA对全身血流动力学没有影响。我们得出结论，3-NPA通过开放线粒体K(ATP)通道诱导持久的抗缺血作用。
