Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury
Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury
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DOI：
10.1073/pnas.96.25.14617
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发表时间：
1999-12-07
影响因子：
11.1
通讯作者：
Feelisch, M
中科院分区：
文献类型：
--
作者：
Ma, XL;Cao, F;Feelisch, M
最近的实验证据表明，活性氮氧化物物种可以显着促进缺血后心肌损伤。本研究的目的是评价两种活性氮氧化物，硝酰基（NO-）和一氧化氮（NO-），在心肌缺血和再灌注损伤的作用。家兔局部心肌缺血45分钟，再灌注180分钟。再灌注前5分钟静脉注射溶剂（0.9%NaCl）、1 μ mol/kg 5-亚硝基谷胱甘肽（GSNO）和3 μ mol/kg安杰利盐（AS）。用GSNO治疗显著减弱再灌注损伤，如通过改善心脏功能、降低血浆肌酸激酶活性、减小坏死尺寸和降低心肌髓过氧化物酶活性所证明的。与此相反，AS在血流动力学等效剂量的管理，不仅没有衰减，而是加重再灌注损伤，左心室舒张末期压，心肌肌酸激酶释放和坏死的大小增加。分解的AS没有效果。GO-AS与铁氰化物的给药，铁氰化物是一种将NO-转化为NO的单电子氧化剂，完全阻断AS的损伤作用，具有与GSNO相似的心肌保护作用。这些结果表明，虽然NO是保护性的，NO-增加缺血/再灌注期间发生的组织损伤，并表明硝酰基的形成可能有助于缺血后心肌损伤。
Recent experimental evidence suggests that reactive nitrogen oxide species can contribute significantly to postischemic myocardial injury. The aim of the present study was to evaluate the role of two reactive nitrogen oxide species, nitroxyl (NO-) and nitric oxide (NO-), in myocardial ischemia and reperfusion injury. Rabbits were subjected to 45 min of regional myocardial ischemia followed by 180 min of reperfusion. Vehicle (0.9% NaCl), 1 mu mol/kg 5-nitrosoglutathione (GSNO) tan NO. donor), or 3 mu mol/kg Angeli's salt (AS) (a source of NO-) were given i.v. 5 min before reperfusion. Treatment with GSNO markedly attenuated reperfusion injury, as evidenced by improved cardiac function, decreased plasma creatine kinase activity, reduced necrotic size, and decreased myocardial myeloperoxidase activity. In contrast, the administration of AS at a hemodynamically equieffective dose not only failed to attenuate but, rather, aggravated reperfusion injury, indicated by an increased left ventricular end diastolic pressure, myocardial creatine kinase release and necrotic size. Decomposed AS was without effect. Go-administration of AS with ferricyanide, a one-electron oxidant that converts NO- to NO., completely blocked the injurious effects of AS and exerted significant cardioprotective effects similar to those of GSNO. These results demonstrate that, although NO. is protective, NO- increases the tissue damage that occurs during ischemia/reperfusion and suggest that formation of nitroxyl may contribute to postischemic myocardial injury.