title: Airway arginase expression and Nω-hydroxy-nor-arginine effect on methacholine-induced bronchoconstriction differentiate Lewis and Fischer rat strains.
abstract: Innate airway hyperresponsiveness (AHR) is well modeled by two strains of rat, the hyperresponsive Fischer 344 rat and the normoresponsive Lewis rat. Arginase has been implicated in AHR associated with allergic asthma models. We addressed the role of arginase in innate AHR using the Fischer-Lewis model. In vivo arginase inhibition with N(ω)-hydroxy-nor-arginine (nor-NOHA) was evaluated on methacholine-induced bronchoconstriction in the Fischer and the Lewis rats. Arginase activity and mRNA expression were quantified in structural and resident cells of the proximal airway tree. The effect of nor-NOHA was evaluated on cultured tracheal smooth muscle proliferation. Fischer rats exhibited significantly greater changes in respiratory resistance and elastance in response to methacholine compared with Lewis rats. nor-NOHA reduced the methacholine-induced bronchoconstriction in the central airways of Lewis rats, while it did not change the innate AHR of Fischer rats. Lewis rats exhibited greater arginase activity in tracheal smooth muscle but a lower proliferation rate compared with Fischer rats. Smooth muscle proliferation was not affected by nor-NOHA in either strain of rats. The strain-specific arginase expression in the smooth muscle may contribute to the differences in sensitivity of the methacholine challenged airways of Lewis and Fischer rats to inhibition of arginase.
authors: Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors: Paul-André
authors: PA
authors: Risse
authors: Anouk
authors: A
authors: Lavoie-Lamoureux
authors: Taisuke
authors: T
authors: Jo
authors: Kimitake
authors: K
authors: Tsuchiya
authors: Sana
authors: S
authors: Siddiqui
authors: James G
authors: JG
authors: Martin
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D016210:Methacholine Chloride; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013045:Species Specificity
chemical_list: D016085:Bronchoconstrictor Agents; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016210:Methacholine Chloride; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D001119:Arginase
keywords: epithelium; innate hyperresponsivness; nitric oxide synthase; nor-NOHA; smooth muscle