Published ahead of print on May 18, 2006, doi:10.1165/rcmb.2005-0391OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0391OC Effects of Nitric Oxide Synthases in Chronic Allergic Airway Inflammation and RemodelingDepartments of Medicine and Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil Correspondence and requests for reprints should be addressed to Iolanda F. L. C. Tibério, M.D., Ph.D., Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455—Sala 1216, 01246-903, São Paulo, SP, Brazil. E-mail: iocalvo{at}uol.com.br
The precise role of each nitric oxide (NO) synthase (NOS) isoform in the pathobiology of asthma is not well established. Our objective was to investigate the contribution of constitutive NO synthase (cNOS) and inducible NOS (iNOS) isoforms to lung mechanics and inflammatory and remodeling responses in an experimental model of chronic allergic pulmonary inflammation. Guinea pigs were submitted to seven ovalbumin exposures with increasing doses (1
Key Words: collagen deposition • experimental asthma model • nitric oxide This article has been cited by other articles:
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5 mg/ml) for 4 wk. The animals received either chronic L-NAME (N-nitro-L-arginine methyl ester, in drinking water) or 1400W (iNOS-specific inhibitor, intraperitoneal) treatments. At 72 h after the seventh inhalation of ovalbumin solution, animals were anesthetized, mechanically ventilated, exhaled NO was collected, and lung mechanical responses were evaluated before and after antigen challenge. Both L-NAME and 1400W treatments increased baseline resistance and decreased elastance of the respiratory system in nonsensitized animals. After challenge, L-NAME increased resistance of the respiratory system and collagen deposition on airways, and decreased peribronchial edema and mononuclear cell recruitment. Administration of 1400W reduced resistance of the respiratory system response, eosinophilic and mononuclear cell recruitment, and collagen and elastic fibers content in airways. L-NAME treatment reduced both iNOS- and neuronal NOS-positive eosinophils, and 1400W diminished only the number of eosinophils expressing iNOS. In this experimental model, inhibition of NOS-derived NO by L-NAME treatment amplifies bronchoconstriction and increases collagen deposition. However, blockage of only iNOS attenuates bronchoconstriction and inflammatory and remodeling processes. 
