Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury.
Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury.
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DOI：
10.1073/pnas.91.5.1691
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发表时间：
1994-03
影响因子：
11.1
通讯作者：
Luis Yu;P. Gengaro;Michel Niederberger;Thomas J. Burke;Robert W. Schrier
中科院分区：
文献类型：
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作者：
Luis Yu;P. Gengaro;Michel Niederberger;Thomas J. Burke;Robert W. Schrier
一氧化氮（NO），除其他几个功能，可能在缺氧和复氧损伤中发挥作用，由于其自由基的性质和高反应性与超氧自由基产生过氧亚硝酸盐，氧化剂分子。本研究进行了评估一个潜在的作用，无论是内源性或外源性的，在缺氧/复氧（H/R）的模型在新鲜分离的大鼠近端小管。通过L-[3 H]精氨酸转化为L-[3 H]瓜氨酸评估，在含氧量正常的肾小管中检测到NO合酶活性。该活性可被NO合成酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME）抑制，并被缺氧15 min所刺激。近端小管缺氧15分钟，然后再给氧35分钟所造成的损伤完全防止由L-NAME的乳酸脱氢酶的释放，而D-NAME，它不抑制NO合酶，没有影响。而NO底物L-精氨酸（L-arginine，L-arginine）则增强H/R损伤。这些影响被亚硝酸盐/硝酸盐的产生所抵消。在单独的实验中，除了硝普钠，一氧化氮供体，近端小管增强H/R损伤，这种效果可以被血红蛋白，一氧化氮清除剂阻断。此外，加入硝普钠逆转了L-NAME对H/R损伤的保护作用。这些结果表明，NO在大鼠近端肾小管合成，并参与大鼠肾小管H/R损伤的介质之一。
Nitric oxide (NO), among several other functions, may play a role in hypoxia and reoxygenation injury due to its free radical nature and high reactivity with the superoxide radical to yield peroxynitrite, an oxidant molecule. The present study was undertaken to evaluate a potential role for NO, either endogenous or exogenous, in a model of hypoxia/reoxygenation (H/R) in freshly isolated rat proximal tubules. NO synthase activity, as assessed by conversion of L-[3H]arginine to L-[3H]citrulline, was detected in normoxic tubules. This activity could be inhibited by N-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, and was stimulated by 15 min of hypoxia. The injury in proximal tubules caused by 15 min of hypoxia followed by 35 min of reoxygenation was completely prevented by L-NAME as assessed by release of lactate dehydrogenase, whereas D-NAME, which does not inhibit NO synthase, had no effect. In contrast, L-arginine (NO substrate) enhanced the H/R injury. These effects were paralleled by nitrite/nitrate production. In separate experiments, the addition of sodium nitroprusside, a NO donor, to proximal tubules enhanced the H/R injury; this effect could be blocked by hemoglobin, a NO scavenger. Also, addition of nitroprusside reversed L-NAME protection against H/R injury. These results demonstrate that NO is synthesized in rat proximal tubules and participates as one of the mediators in rat tubular H/R injury.