Ma X L, Weyrich A S, Lefer D J, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799.
Circ Res. 1993 Feb;72(2):403-12. doi: 10.1161/01.res.72.2.403.
We measured changes in basal release of nitric oxide and its effect on polymorphonuclear leukocyte (PMN) adherence to endothelial cells (ECs) in a feline model of myocardial ischemia (90 minutes) and reperfusion. Basal release of nitric oxide from the left anterior descending coronary artery (LAD) after myocardial ischemia/reperfusion and from the control left circumflex coronary artery (LCX) was assessed by NG-nitro L-arginine methyl ester (L-NAME)-induced vasocontraction. L-NAME induced a significant EC-dependent vasocontraction in control LCX rings (0.28 +/- 0.04 g), which was fully reversed by L-arginine but not D-arginine. L-NAME-induced vasocontraction of LAD rings was not significantly changed after 90 minutes of myocardial ischemia without reperfusion. However, 10 minutes of reperfusion reduced the L-NAME-induced vasocontraction to 0.13 +/- 0.04 g (p < 0.05), and this was restored by addition of 3 mM L-arginine but not D-arginine. Longer periods of reperfusion progressively decreased L-NAME-induced vasocontraction. After 270 minutes of reperfusion, L-NAME-induced vasocontraction was virtually abolished. Myocardial ischemia without reperfusion did not increase PMN adherence to ECs. However, PMN adherence to LAD ECs was significantly increased after 20 minutes of reperfusion (39 +/- 6 to 105 +/- 9 PMNs/mm2, p < 0.01), and incubation of LAD segments with L-arginine significantly attenuated this increase in PMN adherence. After 270 minutes of reperfusion, PMN adherence to LAD ECs was further increased to 224 +/- 10 PMNs/mm2 (p < 0.001). This increase in PMN adherence was almost completely blocked by MAb R15.7, a monoclonal antibody against CD18 of PMNs, and was significantly attenuated by MAb RR1/1, a monoclonal antibody against intercellular adhesion molecule-1 of ECs (p < 0.01). These results indicate that decreased basal release of endothelium-derived relaxing factor after myocardial ischemia/reperfusion precedes enhanced PMN adherence to the coronary endothelium, which may lead to PMN-induced myocardial injury.
在猫心肌缺血（90分钟）及再灌注模型中，我们测定了一氧化氮基础释放量的变化及其对多形核白细胞（PMN）黏附于内皮细胞（ECs）的影响。通过NG-硝基-L-精氨酸甲酯（L-NAME）诱导的血管收缩来评估心肌缺血/再灌注后左前降支冠状动脉（LAD）及对照左旋冠状动脉（LCX）中一氧化氮的基础释放量。L-NAME在对照LCX环中诱导出显著的内皮细胞依赖性血管收缩（0.28±0.04克），L-精氨酸可使其完全逆转，而D-精氨酸则不能。在无再灌注的90分钟心肌缺血后，L-NAME诱导的LAD环血管收缩无显著变化。然而，10分钟的再灌注使L-NAME诱导的血管收缩降至0.13±0.04克（p<0.05），添加3 mM L-精氨酸可使其恢复，而D-精氨酸则不能。更长时间的再灌注会使L-NAME诱导的血管收缩逐渐降低。再灌注270分钟后，L-NAME诱导的血管收缩几乎消失。无再灌注的心肌缺血未增加PMN对ECs的黏附。然而，再灌注20分钟后，PMN对LAD ECs的黏附显著增加（从39±6至105±9个PMN/mm²，p<0.01），用L-精氨酸孵育LAD节段可显著减弱PMN黏附的这种增加。再灌注270分钟后，PMN对LAD ECs的黏附进一步增加至224±10个PMN/mm²（p<0.001）。PMN黏附的这种增加几乎完全被抗PMN CD18的单克隆抗体MAb R15.7阻断，并被抗ECs细胞间黏附分子-1的单克隆抗体MAb RR1/1显著减弱（p<0.01）。这些结果表明，心肌缺血/再灌注后内皮源性舒张因子基础释放量的降低先于PMN对冠状动脉内皮黏附的增强，这可能导致PMN诱导的心肌损伤。
