Effects of acute and chronic nitric oxide inhibition in an experimental model of chronic pulmonary allergic inflammation in guinea pigs

Departments of 1 Medicine and 2 Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil Submitted 7 January 2005 ; accepted in final form 31 May 2005 Endogenously produced nitric oxide is a recognized regulator of physiological lung events, such as a neurotransmitter and a proinflammatory mediator. We tested the differences between chronic and acute nitric oxide inhibition by N -nitro- L -arginine methyl ester ( L -NAME) treatment in lung mechanics, inflammation, and airway remodeling in an experimental asthma model in guinea pigs. Both acute and chronic L -NAME treatment reduced exhaled nitric oxide in sensitized animals ( P < 0.001). Chronic L -NAME treatment increased baseline and maximal responses after antigen challenge of respiratory system resistance and reduced peribronchial edema and mononuclear cells airway infiltration ( P < 0.05). Acute administration of L -NAME increased maximal values of respiratory system elastance and reduced mononuclear cells and eosinophils in airway wall ( P < 0.05). Chronic ovalbumin exposure resulted in airway wall thickening due to an increase in collagen content ( P < 0.005). Chronic nitric oxide inhibition increased collagen deposition in airway wall in sensitized animals ( P < 0.05). These data support the hypothesis that in this model nitric oxide acts as a bronchodilator, mainly in proximal airways. Furthermore, chronic nitric oxide inhibition was effective in reducing edema and mononuclear cells in airway wall. However, airway eosinophilic inflammation was unaltered by chronic L -NAME treatment. In addition, nitric oxide inhibition upregulates collagen deposition in airway walls. experimental models of asthma; N -nitro- L -arginine methyl ester; respiratory mechanics; airway collagen Address for reprint requests and other correspondence: I. C. Tibério, 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 )