The Role of Inducible Nitric Oxide Synthase in the Development of Nasal Hyper-responsiveness of the Rhinosinusitis Rat Model

Kim, Jin Pyeong; Jeon, Sea Yuong; Ahn, Seong Ki; Hwang, Won Hyo; Sung, Byung Gi; Kim, Eun Ah

Abstract

BACKGROUND AND OBJECTIVES
Hyper-responsiveness to nonspecific stimuli is a characteristic finding of all allergic diseases. It is probably due to eosinophil infiltration, release of cytotoxic proteins, and epithelial damage in the airway mucosa. However, the whole mechanism has not been clearly established. We aimed to understand the role of inducible nitric oxide synthase (iNOS) expression in nasal hyper-responsiveness of rhinosinusitis. MATERIALS AND METHOD: 1) To develop a platelet activating factor (PAF)-induced rhinosinusitis rat model, 50 micro liter of 16 micro gram/ml PAF was applied into the nose of rats. At days 1, 3 and 5, the rats were killed. 2) To demonstrate the hyper-responsiveness to topically applied capsaicin, 30 micro liter of 10 micro M capsaicin was applied intranasally and the amount of microvascular leakage in the nasal mucosa was measured with Evans blue assay at days 1, 3 and 5 in the rhinosinusitis model and the control rats. 3) To examine the effect of iNOS, 75 mg/kg of aminoguanidine was pretreated systemically 1 hour before the application of capsaicin. 4) To localize the expression of iNOS, immunohistochemical staining was performed using the avidin-biotin-peroxidase method with an anti-iNOS antibody. RESULTS: Induction of rhinosinusitis by application of PAF was confirmed with histology. A significant infiltration of eosinophils and loss of the epithelium, varied according to the time interval, were observed. A significant enhancement of microvascular leakage was clearly demonstrated by topically applied capsaicin, which was completely blocked by aminoguanidine, the iNOS inhibitor in the PAF-induced rhinosinusitis. The expression of iNOS was localized in the inflammatory cells infiltrated in the mucosa. CONCLUSION: The expression of iNOS in the inflammatory cells as well as epithelial damage related to eosinophil infiltration may cause nasal hyper-responsiveness.