Marteus H, Mavropoulos A, Palm J P, Ulfgren A-K, Bergström J, Alving K
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Nitric Oxide. 2004 Nov;11(3):247-55. doi: 10.1016/j.niox.2004.09.006.
Cigarette smoking reduces the level of nitric oxide (NO) in exhaled air by an unknown mechanism. The view that part of the effect of cigarette smoking on NO production should occur in the oropharyngeal tract is supported by several studies. We have therefore compared smokers and non-smokers regarding non-enzymatic formation of NO from nitrite in the oral cavity since this is a primary candidate target for cigarette smoke. We have also looked at NO synthase-dependent NO formation in the mucosa of the oropharyngeal tract as an alternative target for the inhibitory effect induced by cigarette smoke. Smokers exhaled 67% lower levels of NO than controls (p<0.01, n=15 each group). We could not detect any significant difference in salivary nitrite, nitrate or ascorbate between smokers and non-smokers. Mouthwash with the antibacterial agent chlorhexidine reduced salivary nitrite (-65%) and exhaled NO levels (-10%) similarly in the two groups. Immunohistochemical techniques revealed dense expression of inducible (but not endothelial or neuronal) NO synthase in the squamous epithelium of non-inflamed tonsillar and gingival tissue biopsies. In the same biopsies, significant Ca2+ -independent citrulline-forming activity was detected. We found no difference between smoking and non-smoking subjects regarding NO-synthase expression and in vitro activity. In another group of non-smoking subjects (n=10), spraying the oropharyngeal tract with the NO-synthase inhibitor NG-monomethyl-L-arginine (250 mg) significantly reduced exhaled NO levels for at least 30 min (-18%, p<0.01). Our data suggest that cigarette smoking does not affect non-enzymatic NO formation from nitrite in saliva. However, NO is also formed by inducible NO synthase in the squamous epithelium of the normal oropharyngeal tract. We suggest that cigarette smoking may down-regulate enzymatic NO formation in the oropharyngeal compartment as well as in the bronchial compartment.
吸烟通过未知机制降低呼出气体中的一氧化氮（NO）水平。多项研究支持这样一种观点，即吸烟对NO产生的部分影响应发生在口咽道。因此，我们比较了吸烟者和非吸烟者口腔中亚硝酸盐非酶促形成NO的情况，因为这是香烟烟雾的主要候选靶标。我们还研究了口咽道黏膜中一氧化氮合酶依赖性NO的形成，将其作为香烟烟雾诱导抑制作用的另一个靶标。吸烟者呼出的NO水平比对照组低67%（p<0.01，每组n = 15）。我们未检测到吸烟者和非吸烟者唾液中亚硝酸盐、硝酸盐或抗坏血酸盐有任何显著差异。两组使用抗菌剂氯己定漱口后，唾液亚硝酸盐（-65%）和呼出NO水平（-10%）的降低情况相似。免疫组织化学技术显示，在未发炎的扁桃体和牙龈组织活检标本的鳞状上皮中，诱导型（而非内皮型或神经型）一氧化氮合酶有密集表达。在相同的活检标本中，检测到显著的非钙依赖性瓜氨酸形成活性。我们发现吸烟和非吸烟受试者在一氧化氮合酶表达和体外活性方面没有差异。在另一组非吸烟受试者（n = 10）中，向口咽道喷洒一氧化氮合酶抑制剂NG-单甲基-L-精氨酸（250 mg）可使呼出NO水平在至少30分钟内显著降低（-18%，p<0.01）。我们的数据表明，吸烟不影响唾液中亚硝酸盐非酶促形成NO。然而，正常口咽道鳞状上皮中的诱导型一氧化氮合酶也可形成NO。我们认为，吸烟可能会下调口咽腔以及支气管腔中酶促NO的形成。
