Published ahead of print on May 18, 2006, doi:10.1165/rcmb.2005-0391OC Am. J. Respir. Cell Mol. Biol., Volume 35, Number 4, October 2006, 457-465 A more recent version of this article appeared on October 1, 2006
Submitted on October 18, 2005 Effects of Nitric Oxide Synthases in Chronic Allergic Airway Inflammation and RemodelingCarla M Prado1,1 Department of Medicine, School of Medicine - University of Sao Paulo, Sao Paulo, SP, Brazil, 2 Department of Pathology, School of Medicine - University of Sao Paulo, Sao Paulo, SP, Brazil * To whom correspondence should be addressed. E-mail: iocalvo{at}uol.com.br.
Rationale: The precise role of each nitric oxide synthase isoforms (NOS) in the pathobiology of asthma is not well established. Objective: To investigate the contribution of constitutive (cNOS) and inducible (iNOS) isoforms to lung mechanics, inflammatory and remodeling responses in an experimental model of chronic allergic pulmonary inflammation. Methods: Guinea pigs were submitted to seven ovalbumin exposures with increasing doses (1~5 mg/mL) for four weeks. The animals received either chronic L-NAME (N-nitro-L-arginine methyl ester, in drinking water) or 1400W (iNOS specific inhibitor, i.p.) treatments. Seventy-two hours after the seventh inhalation of ovalbumin solution, animals were anesthetized, mechanically ventilated, exhaled nitric oxide was collected and lung mechanical responses were evaluated before and after antigen challenge. Results: Both L-NAME and 1400W treatments increased baseline resistance and decreased elastance of the respiratory system in non-sensitized 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. Conclusions: In this experimental model, inhibition of NOS-derived NO by L-NAME treatment potentates bronchoconstriction and increases the collagen deposition. However, blockage of only iNOS attenuates bronchoconstriction, and inflammatory and remodeling processes.
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