title: Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness.
abstract: For many years it has been supposed that the production of an excess of nitric oxide (NO) by inducible NO synthase (iNOS) plays a major role in inflammatory diseases, including asthma. However, recent studies indicate that a deficiency of beneficial, bronchodilating constitutive NOS (cNOS)-derived NO is important in allergen-induced airway hyperresponsiveness. Although several mechanisms are proposed to explain the reduction of cNOS activity, reduced substrate availability, caused by a combination of increased arginase activity and decreased cellular uptake of L-arginine, appears to play a key role. Recent evidence also indicates that iNOS-induced pathophysiological effects involve substrate deficiency. Thus, at low concentrations of L-arginine iNOS produces both NO and superoxide anions, which results in the increased synthesis of the highly reactive, detrimental oxidant peroxynitrite. Based on these observations, we propose that a relative deficiency of NO caused by increased arginase activity and altered L-arginine homeostasis is a major factor in the pathology of asthma.
authors.affiliation: Department of Molecular Pharmacology, University Centre for Pharmacy, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. h.meurs@farm.rug.nl
authors.forename: Herman
authors.initials: H
authors.lastname: Meurs
authors.forename: Harm
authors.initials: H
authors.lastname: Maarsingh
authors.forename: Johan
authors.initials: J
authors.lastname: Zaagsma
mesh_terms: D000818:Animals; D001119:Arginase / Q000502:physiology*; D001249:Asthma / Q000201:enzymology* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism; D017942:Nitric Acid / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D017942:Nitric Acid; D019001:Nitric Oxide Synthase; D001119:Arginase; D009584:Nitrogen