IDENTIFICATION OF ARGININE AS A PRECURSOR OF ENDOTHELIUM-DERIVED RELAXING FACTOR
IDENTIFICATION OF ARGININE AS A PRECURSOR OF ENDOTHELIUM-DERIVED RELAXING FACTOR
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DOI：
10.1073/pnas.85.22.8664
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发表时间：
1988-11-01
影响因子：
11.1
通讯作者：
LEVI, R
中科院分区：
文献类型：
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作者：
SAKUMA, I;STUEHR, DJ;LEVI, R
一氧化氮（NO）是一种主要的内皮源性松弛因子（EDRF），在血管舒张胺、肽、蛋白质、离子载体和核苷酸的作用下释放。EDRF是平滑肌张力和血小板聚集和粘附的重要调节因子。在无氨基酸培养基中，组胺和乙酰胆碱通过edrf依赖机制使完整的去甲肾上腺素收缩的豚鼠肺动脉松弛。N.omega。-单甲基精氨酸（n - meg; 0.25 mM）抑制了64-73%的弛豫。N-MeArg的抑制作用发展迅速，过量的l -精氨酸立即完全逆转了N-MeArg的抑制作用，而过量的d -精氨酸和瓜氨酸则没有。N-MeArg不减少硝普苷（no生成剂）引起的松弛，表明N-MeArg作用于内皮细胞而非平滑肌。这些观察结果有力地表明，在完整的豚鼠肺动脉中，EDRF起源于内源性精氨酸池的胍氮(s)的酶促作用。这与活化巨噬细胞中活性氮中间体的起源惊人地相似。
Nitric oxide (NO) is a major endothelium-derived relaxing factor (EDRF) released in response to vasodilating amines, peptides, proteins, ionophores, and nucleotides. EDRF is an important regulator of smooth muscle tone and platelet aggregation and adhesion. Histamine and acetylcholine relax the intact norepinephrine-constricted guinea pig pulmonary artery by an EDRF-dependent mechanism in a medium free of amino acids. N.omega.-Monomethylarginine (N-MeArg; 0.25 mM) inhibited this relaxation by 64-73%. Inhibition by N-MeArg developed rapidly and was immediately and completed reversed by excess L-arginine but not by D-arginine or by citrulline. N-MeArg did not diminish relaxation induced by nitroprusside, an NO-generating agent, indicating that N-MeArg acts on endothelium rather than on smooth muscle. These observations strongly suggest that, in the intact guinea pig pulmonary artery, EDRF originates from enzymatic action on the guanido nitrogen(s) of an endogenous pool of arginine. This is strikingly similar to the origin of reactive nitrogen intermediates in activated macrophages.