title: Nitric oxide synthase inhibition augments acute allergic reactions in the pig airways in vivo.
abstract: The aim of this study was to examine the effects of nitric oxide synthase inhibition on antigen- and histamine-induced acute airway reactions, in order to clarify the possible modulating role of NO. Twelve specific-pathogen-free pigs (sensitized with Ascaris suum antigen) were challenged with an antigen aerosol during mechanical ventilation and anaesthesia. Six pigs were pretreated with N(G)-nitro-L-arginine (L-NA, 10 mg x kg(-1)), a NO synthase inhibitor, 30 min before challenge. In separate experiments, seven sensitized pigs received histamine (5 mg) aerosols before and after L-NA treatment. It was found that pretreatment with L-NA resulted in an enhanced airways resistance response to antigen (areas under the curve 0-90 min were (mean+/-SEM) 1,119+/-160 versus 555+/-56 (cmH2O x L(-1) x s(-1) x min for controls, p<0.05 (Mann-Whitney U-test), whereas this response to histamine was not affected by L-NA. Moreover, L-NA pretreatment significantly enhanced total protein (1.85+/-0.43 versus 0.31+/-0.06 g x L(-1), p<0.01) and histamine levels (42.8+/-16.0 versus 2.6+/-0.8 nM, p<0.05) in bronchoalveolar lavage fluid 45 min after antigen challenge. In conclusion, this study showed that N(G)-nitro-L-arginine enhanced reactions occurring during the acute allergic reaction in pigs in vivo. This indicates a protective role of nitric oxide, which might occur through downregulation of histamine release from mast cells rather than a direct bronchodilating effect of nitric oxide.
authors.affiliation: Dept of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: R J
authors.initials: RJ
authors.lastname: Middelveld
authors.forename: W C
authors.initials: WC
authors.lastname: Zetterquist
authors.forename: D
authors.initials: D
authors.lastname: Bergman
authors.forename: K
authors.initials: K
authors.lastname: Alving
mesh_terms: D000208:Acute Disease; D000403:Airway Resistance; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology; D001980:Bronchi / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002319:Cardiovascular System / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005740:Gases / Q000097:blood; D006632:Histamine / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000032:analysis / Q000652:urine; D008170:Lung Compliance; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D013552:Swine
chemical_list: D000947:Antigens, Helminth; D004791:Enzyme Inhibitors; D005740:Gases; D018836:Inflammation Mediators; D019335:Nitroarginine; D006632:Histamine; D019001:Nitric Oxide Synthase