[Detection of nitric oxide synthases in physiological and pathophysiological processes of the nasal mucosa].

Nitric oxide (NO) can play an important role in the regulation of vascular tone and neurotransmission, as well as in non-specific immunoreactions and inflammation in a variety of tissues. Increased quantities of nitric oxide in respired air can be measured during inflammatory processes. However, the exact role and precise sources of NO under physiological and pathophysiological conditions within the airways remain to be defined. Three isoforms of NO-synthases can be distinguished: two constitutive (neuronal and endothelial) Ca(2+)-dependent cNOS and one inducible Ca(2+)-independent iNOS (NOS II). Constitutive NOS (NOS I and III) release a basal amount of NO under physiological conditions. The inducible form once expressed can catalyse the generation of large quantities of NO. Many kinds of cells, such as macrophages, neutrophils, endothelium and smooth muscle cells, are capable of expressing NOS II. Since all isoforms of NO-synthase seem to be present in nasal tissues and the expression of iNOS under inflammatory conditions seems to be responsible for excessive production of NO, the distribution of NOS-isoforms (especially NOS II) in normal and inflammatory nasal tissue, as well as the exact requirements for expression of iNOS remain to be proven. Non-inflamed fresh human nasal mucosa from the middle turbinate was compared immuno-histologically with nasal mucosa having the typical findings of chronic polypoid rhinosinusitis (i.e., polypoid middle turbinates and polyps of the middle nasal duct). In order to gain more information about the mechanisms of acute inflammation, non-inflamed vital turbinates were incubated in vitro with the proinflammatory substances bacterial lipopolysaccharides (LPS) and tumor necrosis-factor (TNF) for 30, 60, 90, 120, 180 and 240 min. Subsequent to exposure to NADPH-diaphorase and immunostaining with specific antibodies to each NOS-isoform, clearly increased or initiated expressions of inducible NOS (iNOS) in blood vessels, glands, macrophages and epithelium of chronically inflamed and LPS-incubated nasal tissue became apparent in comparison to the non-inflamed controls. In contrast, NOS III/NOS I seemed to be not affected. The onset of immunohistochemically recognizable NOS II expression was observed after 90 min incubation with of LPS/TNF-alpha. Polypoid tissue showed a strong increase in submucosal thickness and a high infiltration of iNOS-positive leukocytes (granulocytes and macrophages) compared to the LPS-incubated non-inflamed specimens. These findings implicate NOS II generated nitric oxide as a key agent for causing swelling, secretion and obstruction in patients with acute and chronic polypoid or allergic rhinitis. These findings also suggest that molecular NO has to be considered in the pathophysiology of chronic polypoid rhinosinusitis.