Inorganic nitrate is a possible source for systemic generation of nitric oxide
Inorganic nitrate is a possible source for systemic generation of nitric oxide
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DOI：
10.1016/j.freeradbiomed.2004.04.027
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发表时间：
2004-08-01
影响因子：
7.4
通讯作者：
Govoni, M
中科院分区：
文献类型：
--
作者：
Lundberg, JO;Govoni, M
硝酸盐和亚硝酸盐被认为是一氧化氮（NO）的稳定的非活性终产物。虽然最近的几项研究表明亚硝酸盐可以再次还原为生物活性NO，但更稳定的阴离子硝酸盐仍然被认为是生物惰性的。硝酸盐集中在唾液中，其中一部分被细菌硝酸盐还原酶还原为亚硝酸盐。我们测试了摄入无机硝酸盐是否会影响唾液和全身亚硝酸盐和S-亚硝基硫醇的水平，两者都被认为是NO的循环储存池。在摄入硝酸钠（10 mg/kg）之前和之后，在血浆、唾液和尿液中测量硝酸盐、亚硝酸盐和S-亚硝基硫醇的水平。硝酸盐负荷后，唾液、血浆和尿液中的硝酸盐水平大大增加。唾液中的S-亚硝基硫醇也增加，但血浆水平保持不变。硝酸盐摄入后，血浆亚硝酸盐增加了4倍。然而，如果受试者在硝酸盐负荷后避免吞咽，则血浆亚硝酸盐的增加被阻止，从而说明其唾液来源。我们表明，硝酸盐是一个基板系统生成的亚硝酸盐。有几种途径可以进一步将亚硝酸盐还原为NO。这些结果挑战了硝酸盐是生物惰性的教条，而是表明存在一种从硝酸盐生成NO的完全反向途径。(C)2004年爱思唯尔公司All rights reserved.
Nitrate and nitrite have been considered stable inactive end products of nitric oxide (NO). While several recent studies now imply that nitrite can be reduced to bioactive NO again, the more stable anion nitrate is still considered to be biologically inert. Nitrate is concentrated in saliva, where a part of it is reduced to nitrite by bacterial nitrate reductases. We tested if ingestion of inorganic nitrate would affect the salivary and systemic levels of nitrite and S-nitrosothiols, both considered to be circulating storage pools for NO. Levels of nitrate, nitrite, and S-nitrosothiols were measured in plasma, saliva, and urine before and after ingestion of sodium nitrate (10 mg/kg). Nitrate levels increased greatly in saliva, plasma, and urine after the nitrate load. Salivary S-nitrosothiols also increased, but plasma levels remained unchanged. A 4-fold increase in plasma nitrite was observed after nitrate ingestion. If, however, the test persons avoided swallowing after the nitrate load, the increase in plasma nitrite was prevented, thereby illustrating its salivary origin. We show that nitrate is a substrate for systemic generation of nitrite. There are several pathways to further reduce this nitrite to NO. These results challenge the dogma that nitrate is biologically inert and instead suggest that a complete reverse pathway for generation of NO from nitrate exists. (C) 2004 Elsevier Inc. All rights reserved.