Effects of chronic L-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation.
The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by N(omega)-nitro-L-arginine methyl ester (L-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1 approximately 5 mg/ml for 4 wk) and treated or not with L-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF(2alpha) expression in the alveolar septa compared with controls (P<0.05). L-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses (P<0.01), nNOS- and iNOS-positive cells, elastic fiber content (P<0.001), and isoprostane-8-PGF(2alpha) in the alveolar septa (P<0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.
Angeli
Patrícia
P
Department of Medicine, School of Medicine, University of Sao Paulo, São Paulo, Brazil.
Prado
Carla M
CM
Xisto
Débora G
DG
Silva
Pedro L
PL
Pássaro
Caroline P
CP
Nakazato
Hugo D
HD
Leick-Maldonado
Edna A
EA
Martins
Milton A
MA
Rocco
Patricia R M
PR
Tibério
Iolanda F L C
IF
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D006168:Guinea Pigs; D008168:Lung / Q000166:cytology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D011014:Pneumonia / Q000503:physiopathology*
D019331:NG-Nitroarginine Methyl Ester