SUPEROXIDE ANIONS AND HYPEROXIA INACTIVATE ENDOTHELIUM-DERIVED RELAXING FACTOR

SUPEROXIDE ANIONS AND HYPEROXIA INACTIVATE ENDOTHELIUM-DERIVED RELAXING FACTOR
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DOI:
10.1152/ajpheart.1986.250.5.h822
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发表时间:
1986-05-01
影响因子:
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通讯作者:
VANHOUTTE, PM
VANHOUTTE, PM
中科院分区:
其他
文献类型:
--
作者:
RUBANYI, GM;VANHOUTTE, PM

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实验旨在确定氧源性自由基对内皮源性松弛因子或乙酰胆碱释放因子的产生和生物活性的影响。将无内皮的犬冠状动脉环(生物测定环)与通过有内皮的犬股动脉的溶液混合。超氧化物歧化酶在股动脉上游而非下游注入时引起生物测定环的最大松弛;过氧化氢酶抑制了超氧化物歧化酶的这种作用。输注乙酰胆碱可使生物测定环松弛,因为它能从内皮细胞释放一种或多种不稳定的松弛因子。当注入股动脉下方时,超氧化物歧化酶和过氧化氢酶在较小程度上增强了对乙酰胆碱的松弛。超氧化物歧化酶,而不是过氧化氢酶,使内皮来源的松弛因子的半衰期增加了一倍。通过将灌注液的氧含量从95%降低到10%,酶的这种保护作用增强了五倍。这些数据表明:(1)超氧阴离子使内皮细胞中乙酰胆碱释放的松弛因子失活;(2)高氧有利于内皮源性松弛因子的失活。
Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: (1) superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and (2) hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).