Effects of acute and chronic nitric oxide inhibition in an experimental model of chronic pulmonary allergic inflammation in guinea pigs.
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(omega)-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.
Prado
Carla M
CM
Department of Medicine, University of São Paulo, Brazil.
Leick-Maldonado
Edna A
EA
Kasahara
David I
DI
Capelozzi
Vera L
VL
Martins
Milton A
MA
Tibério
Iolanda F L C
IF
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology / Q000503:physiopathology*; D011654:Pulmonary Edema / Q000276:immunology / Q000503:physiopathology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D010047:Ovalbumin; D003094:Collagen; D019331:NG-Nitroarginine Methyl Ester