title: Effects of inducible nitric oxide synthase inhibition in bronchial vascular remodeling-induced by chronic allergic pulmonary inflammation.
abstract: Vascular remodeling is an important feature in asthma pathophysiology. Although investigations suggested that nitric oxide (NO) is involved in lung remodeling, little evidence established the role of inducible NO synthase (iNOS) isoform in bronchial vascular remodeling. The authors investigated if iNOS contribute to bronchial vascular remodeling induced by chronic allergic pulmonary inflammation. Guinea pigs were submitted to ovalbumin exposures with increasing doses (1∼5 mg/mL) for 4 weeks. Animals received 1400W (iNOS-specific inhibitor) treatment for 4 days beginning at 7th inhalation. Seventy-two hours after the 7th inhalation, animals were anesthetized, mechanical ventilated, exhaled NO was collected, and lungs were removed and submitted to picrosirius and resorcin-fuchsin stains and to immunohistochemistry for matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-β (TGF-β). Collagen and elastic fiber deposition as well as MMP-9, TIMP-1, and TGF-β expression were increase in bronchial vascular wall in ovalbumin-exposed animals. The iNOS inhibition reduced all parameters studied. In this model, iNOS inhibition reduced the bronchial vascular extracellular remodeling, particularly controlling the collagen and elastic fibers deposition in pulmonary vessels. This effect can be associated to a reduction on TGF-β and on metalloproteinase-9/TIMP-1 vascular expression. It reveals new therapeutic strategies and some possible mechanism related to specific iNOS inhibition to control vascular remodeling.
authors.affiliation: Department of Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Carla Máximo
authors.initials: CM
authors.lastname: Prado
authors.forename: Larissa
authors.initials: L
authors.lastname: Yano
authors.forename: Guilherme
authors.initials: G
authors.lastname: Rocha
authors.forename: Claudia Miranda
authors.initials: CM
authors.lastname: Starling
authors.forename: Vera Luíza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Edna Aparecida
authors.initials: EA
authors.lastname: Leick-Maldonado
authors.forename: Mílton de Arruda
authors.initials: Mde A
authors.lastname: Martins
authors.forename: Iolanda F Lopes Calvo
authors.initials: IF
authors.lastname: Tibério
mesh_terms: D000280:Administration, Inhalation; D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000378:metabolism; D001596:Benzylamines / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004547:Elastic Tissue / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D010047:Ovalbumin; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9