Deng Xin-Sheng, Deitrich Richard A
University of Colorado Health Sciences Center at Fitzsimons, Department of Pharmacology, Alcohol Research Center, Aurora, CO 80045-6508, USA.
Curr Clin Pharmacol. 2007 May;2(2):145-53. doi: 10.2174/157488407780598135.
Ethanol (EtOH) in alcoholic beverages is consumed by a large number of individuals and its elimination is primarily by oxidation. The role of nitric oxide (NO) in EtOH's effects is important since NO is one of the most prominent biological factors in mammals. NO is constantly formed endogenously from L-arginine. Dose and length of EtOH exposure, and cell type are the main factors affecting EtOH effects on NO production. Either acute or chronic EtOH ingestion affects inducible NO synthase (iNOS) activity. However it seems that EtOH suppresses induced-NO production by inhibition of iNOS in different cells. On the other hand, it is clear that acute low doses of EtOH increase both the release of NO and endothelial NOS (eNOS) expression, and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelial functions. EtOH selectively affects neuronal NOS (nNOS) activity in different brain cells, which may relate to various behavioral interactions. Therefore, there is an excellent chance for EtOH and NO to react with each other. Effects of EtOH on NO production and NOS activity may be important to EtOH modification of cell or organ function. Nitrosated compounds (alkyl nitrites) are often found as the interaction products, which might be one of the minor pathways of EtOH metabolism. NO also inhibits EtOH metabolizing enzymes. Furthermore, NO is involved in EtOH induced liver damage and has a role in fetal development during EtOH exposure in pregnancy. The mechanisms underlying these effects are only partially understood. Hence, the current discussion of the interaction of EtOH and NO is presented.
大量个体饮用含酒精饮料中的乙醇（EtOH），其消除主要通过氧化进行。一氧化氮（NO）在乙醇作用中的角色很重要，因为NO是哺乳动物中最突出的生物因子之一。NO持续由L - 精氨酸内源性生成。乙醇暴露的剂量和时长以及细胞类型是影响乙醇对NO生成作用的主要因素。急性或慢性摄入乙醇都会影响诱导型一氧化氮合酶（iNOS）的活性。然而，乙醇似乎通过抑制不同细胞中的iNOS来抑制诱导型NO的生成。另一方面，很明显急性低剂量乙醇会增加NO的释放以及内皮型一氧化氮合酶（eNOS）的表达，并增强内皮介导的血管舒张，而高剂量则会损害内皮功能。乙醇在不同脑细胞中选择性地影响神经元型一氧化氮合酶（nNOS）的活性，这可能与各种行为相互作用有关。因此，乙醇和NO相互反应的可能性很大。乙醇对NO生成和一氧化氮合酶活性的影响可能对乙醇对细胞或器官功能的调节很重要。亚硝化化合物（亚硝酸烷基酯）常被发现为相互作用产物，这可能是乙醇代谢的次要途径之一。NO还抑制乙醇代谢酶。此外，NO参与乙醇诱导的肝损伤，并在孕期乙醇暴露期间的胎儿发育中起作用。这些作用背后的机制仅部分为人所知。因此，本文对乙醇与NO的相互作用进行了讨论。
