Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation.
Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation.
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DOI：
10.1161/01.cir.94.10.2580
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发表时间：
1996-11
期刊：
影响因子：
37.8
通讯作者：
Yi-wu Xie;M. Wolin
中科院分区：
文献类型：
--
作者：
Yi-wu Xie;M. Wolin
背景一氧化氮（NO）、超氧阴离子（O2·d-）、NO与O2·d-的反应产物、过氧亚硝酸根（ONOO-）和缺血/再灌注均已报道抑制分离的线粒体的呼吸。然而，在完整组织中参与呼吸抑制的特定物种知之甚少。方法和结果采用Clark型电极定量测定小牛离体心肌的耗氧量。外源性和内源性NO来源，从S-亚硝基-N-乙酰青霉胺（SNAP）和缓激肽或卡巴胆碱，可逆地抑制呼吸，而O2。释放剂连苯三酚（PG）抑制呼吸的方式在PG去除15分钟后检测时仅部分逆转。SNAP + PG的ONOO-产生导致O2（-）引起的呼吸抑制在ONOO-产生系统去除15分钟后检测时增强。Tiron（O2的清除剂）没有改变SNAP的作用，但它减弱了PG +/-SNAP的直接抑制作用，并基本上消除了去除O2后15分钟观察到的呼吸抑制。或ONOO生成系统。ONOO-清除剂尿酸仅拮抗PG + SNAP的作用。在将肌肉切片暴露于缺氧（15分钟）和再氧合（10分钟）模型后，观察到呼吸抑制。这种复氧诱导的抑制作用被NO生物合成的底物L-精氨酸增强，并被硝基-L-精氨酸（一种NO合酶抑制剂）、Tiron或尿酸盐显著阻断。结论：NO对心肌呼吸的潜在生理可逆调节在ONOO-形成的条件下转化为不显示快速可逆性的效应，这可能导致缺氧/复氧等情况下的心功能障碍。
BACKGROUND Nitric oxide (NO); superoxide anion (O2.d-); the reaction product of NO with O2.d-, peroxynitrite (ONOO-); and ischemia/reperfusion have all been reported to inhibit respiration in isolated mitochondria. However, the specific species involved in the inhibition of respiration in intact tissues are poorly understood. METHODS AND RESULTS O2 consumption in isolated cardiac muscle from bovine calf hearts was quantified by use of a Clark-type electrode. Exogenous and endogenous sources of NO, from S-nitroso-N-acetylpenicillamine (SNAP) and bradykinin or carbachol, reversibly inhibited respiration, whereas the O2.- releasing agent, pyrogallol (PG), inhibited respiration in a manner that was only partially reversed when examined 15 minutes after the removal of PG. The generation of ONOO- with SNAP + PG caused a potentiation of the O2(-)-elicited inhibition of respiration when examined 15 minutes after the removal of the ONOO- generating system. Tiron (a scavenger of O2.-) did not alter the actions of SNAP, but it attenuated the direct inhibitory effects of PG +/- SNAP and essentially eliminated the suppression of respiration observed 15 minutes after removal of the O2.- or ONOO- generating system. Urate (a scavenger of ONOO-) antagonized only the actions of PG + SNAP. After exposure of muscle slices to a model of hypoxia (15 minutes) and reoxygenation (10 minutes), respiratory inhibition was observed. This reoxygenation-induced inhibition was potentiated by L-arginine, the substrate for NO biosynthesis, and was markedly blocked by nitro-L-arginine (an NO synthase inhibitor), Tiron, or urate. CONCLUSIONS The potentially physiological reversible regulation of respiration in cardiac muscle by NO is converted to an effect that does not show rapid reversibility under conditions in which ONOO- forms, and this could contribute to cardiac dysfunction in situations such as hypoxia/reoxygenation.