Evaluation of the magnitude and rate of nitric oxide production from nitrite in biological systems.
Evaluation of the magnitude and rate of nitric oxide production from nitrite in biological systems.
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DOI：
10.1006/abbi.1998.0785
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发表时间：
1998-09
影响因子：
3.9
通讯作者：
A. Samouilov;P. Kuppusamy;Jay L. Zweier
中科院分区：
文献类型：
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作者：
A. Samouilov;P. Kuppusamy;Jay L. Zweier
近年来研究表明，缺血时生物组织中一氧化氮（NO）的生成增加，并且在酸性条件下，由于组织亚硝酸盐的减少，存在一种不依赖于酶的NO生成途径。为了研究在pH值和亚硝酸盐浓度变化的生物系统中NO生成机制的定量重要性，进行了电子顺磁共振和化学发光研究，以表征亚硝酸盐歧化过程的动力学和强度。推导了亚硝酸盐生成NO的反应过程和相应的速率规律。当pH值从正常的7.4降至缺血组织（如心脏）的酸性值（pH值降至5.5）时，生物组织中典型亚硝酸盐浓度产生和积累NO的量增加了100倍。还观察到，缺血心脏组织含有还原等价物，将亚硝酸盐还原为NO，进一步增加NO形成率40倍以上。在这些条件下，这种不依赖于酶的NO产生的幅度可能超过由一氧化氮合酶的组织浓度产生的幅度。因此，在缺血组织中，亚硝酸盐可能主要是NO的来源而不是产物。
Recently it was shown that the formation of nitric oxide (NO) is increased in biological tissues during ischemia, and that there is an enzyme-independent pathway of NO generation due to reduction of tissue nitrite under the acidic conditions which occur. To investigate the quantitative importance of this mechanism of NO generation in biological systems where pH and nitrite concentrations vary, electron paramagnetic resonance and chemiluminescence studies were performed to characterize the kinetics and magnitude of the nitrite disproportionation process. The reaction process and the corresponding rate law of NO formation from nitrite were derived. The generation and accumulation of NO from typical nitrite concentrations found in biological tissues increased 100-fold when pH decreased from normal values of 7.4 to the acidic values found in ischemic tissues, such as the heart, where pH falls to 5.5. It was also observed that ischemic heart tissue contains reducing equivalents which reduce nitrite to NO, further increasing the rate of NO formation more than 40-fold. Under these conditions the magnitude of this enzyme-independent NO generation may exceed that which can be generated by tissue concentrations of nitric oxide synthase. Thus, in ischemic tissues nitrite can be primarily a source rather than a product of NO.