Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase
Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase
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DOI：
10.1152/ajpheart.1999.276.5.h1567
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发表时间：
1999-05-01
影响因子：
4.8
通讯作者：
Lefer, DJ
中科院分区：
文献类型：
--
作者：
Jones, SP;Girod, WG;Lefer, DJ
心肌缺血再灌注（MI/R）可引起一系列由中性粒细胞（PMN）介导的损伤，其程度受一氧化氮（NO）生物利用度的影响。我们研究了内皮细胞一氧化氮合酶（ecNOS）在心肌梗死/再灌注损伤中的作用，野生型和ecNOS缺陷（-/-）小鼠冠状动脉闭塞20分钟，再灌注120分钟。心肌梗死面积占野生型小鼠缺血区的20.9 ± 2.9%，而ecNOS -/-小鼠的梗死面积明显更大（P < 0.01），占缺血区的46.0 ± 3.8%。由于P-选择素被认为参与了嗜酸性粒细胞介导的I/R损伤的发病机制，我们评估了MYR对野生型和ecNOS -/-小鼠心肌中P-选择素表达的影响。在野生型小鼠MI/R后，用放射性标记的单克隆抗体（MAb）技术测量的P-选择素表达为0.037 +/- 0.009 μ g MAb/g组织，而ecNOS -/-冠状血管系统的特征是显著（P < 0.05）较高的P-选择素表达（0.080 +/- 0.013 μ g MAb/g组织）。缺血后心肌的组织学检查显示，与野生型小鼠（5.0 +/- 0.9 PMN/视野）相比，ecNOS -/-小鼠（29.5 +/- 2.5 PMN/视野）中的中性粒细胞显著（P < 0.01）更多。当野生型和ecNOS -/-小鼠进行30分钟的缺血和120分钟的再灌注时，观察到梗死面积和中性粒细胞积累的类似趋势。这些新的体内研究结果表明，ecNOS衍生的NO在缺血再灌注小鼠心脏的心脏保护作用。
Myocardial ischemia and reperfusion (MI/R) initiates a cascade of polymorphonuclear neutrophil (PMN)-mediated injury, the magnitude of which may be influenced by the bioavailability of nitric oxide (NO). We investigated the role of endothelial cell nitric oxide synthase (ecNOS) in MI/R injury by subjecting wild-type and ecNOS-deficient (-/-) mice to 20 min of coronary artery occlusion and 120 min of reperfusion. Myocardial infarct size represented 20.9 +/- 2.9% of the ischemic zone in wild-type mice, whereas the ecNOS -/- mice had significantly (P < 0.01) larger infarcts measuring 46.0 +/- 3.8% of the ischemic zone. Because P-selectin is thought to be involved with the pathogenesis of neutrophil-mediated I/R injury, we assessed the effects of MYR on P-selectin expression in the myocardium of wild-type and ecNOS -/- mice. P-selectin expression measured with a radiolabeled monoclonal antibody (MAb) technique after MI/R in wild-type mice was 0.037 +/- 0.009 mu g MAb/g tissue, whereas ecNOS -/- coronary vasculature was characterized by significantly (P < 0.05) higher P-selectin expression (0.080 +/- 0.013 mu g MAb/g tissue). Histological examination of the postischemic myocardium revealed significantly (P < 0.01) more neutrophils in the ecNOS -/- (29.5 +/- 2.5 PMN/field) compared with wild-type (5.0 +/- 0.9 PMN/field) mice. A similar trend in infarct size and neutrophil accumulation was observed when wild-type and ecNOS -/- mice were subjected to 30 min of ischemia and 120 min of reperfusion. These novel in vivo findings demonstrate a cardioprotective role for ecNOS-derived NO in the ischemic-reperfused mouse heart.