title: Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation.
abstract: In the present study we evaluated the role of neurokinins in the modulation of inducible nitric oxide synthase (iNOS) inflammatory cell expression in guinea pigs with chronic allergic airway inflammation. In addition, we studied the acute effects of nitric oxide inhibition on this response. Animals were anesthetized and pretreated with capsaicin (50 mg/kg sc) or vehicle 10 days before receiving aerosolized ovalbumin or normal saline twice weekly for 4 wk. Animals were then anesthetized, mechanically ventilated, given normal saline or N(G)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg ic), and challenged with ovalbumin. Prechallenge exhaled NO increased in ovalbumin-exposed guinea pigs (P < 0.05 compared with controls), and capsaicin reduced this response (P < 0.001). Compared with animals inhaled with normal saline, ovalbumin-exposed animals presented increases in respiratory system resistance and elastance and numbers of total mononuclear cells and eosinophils, including those expressing iNOS (P < 0.001). Capsaicin reduced all these responses (P < 0.05) except for iNOS expression in eosinophils. Treatment with l-NAME increased postantigen challenge elastance and restored both resistance and elastance previously attenuated by capsaicin treatment. Isolated l-NAME administration also reduced total eosinophils and mononuclear cells, as well as those cells expressing iNOS (P < 0.05 compared with ovalbumin alone). Because l-NAME treatment restored lung mechanical alterations previously attenuated by capsaicin, NO and neurokinins may interact in controlling airway tone. In this experimental model, NO and neurokinins modulate eosinophil and lymphocyte infiltration in the airways.
authors.affiliation: Department of Medicine, University of São Paulo, School of Medicine, São Paulo, Brazil.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Prado
authors.forename: Edna A
authors.initials: EA
authors.lastname: Leick-Maldonado
authors.forename: Vanessa
authors.initials: V
authors.lastname: Arata
authors.forename: David I
authors.initials: DI
authors.lastname: Kasahara
authors.forename: Mílton A
authors.initials: MA
authors.lastname: Martins
authors.forename: Iolanda F L C
authors.initials: IF
authors.lastname: Tibério
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance; D000818:Animals; D016535:Bronchial Hyperreactivity; D002211:Capsaicin / Q000494:pharmacology; D002908:Chronic Disease; D004548:Elasticity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism; D006168:Guinea Pigs; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015288:Neurokinin A / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000008:administration & dosage
chemical_list: D000336:Aerosols; D004791:Enzyme Inhibitors; D015288:Neurokinin A; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester