Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma

J Allergy Clin Immunol. 2010 Mar;125(3):626-35. doi: 10.1016/j.jaci.2009.10.065. Epub 2010 Feb 11.

Abstract

Background: Disturbance in the delicate balance between L-arginine-metabolizing enzymes such as nitric oxide synthase (NOS) and arginase may lead to decreased L-arginine availability to constitutive forms of NOS (endothelial NOS), thereby increasing the nitro-oxidative stress and airway hyperresponsiveness (AHR).

Objective: In this study, we investigated the effects of high doses of L-arginine on L-arginine-metabolizing enzymes and subsequent biological effects such as cyclic guanosine monophosphate production, lipid peroxidation, peroxynitrite, AHR, and airway inflammation in a murine model of asthma.

Methods: Different doses of L-arginine were administered to ovalbumin-sensitized and challenged mice. Exhaled nitric oxide, AHR, airway inflammation, T(H)2 cytokines, goblet cell metaplasia, nitro-oxidative stress, and expressions of arginase 1, endothelial NOS, and inducible NOS in lung were determined.

Results: L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T(H)2 cytokines, TGF-beta1, goblet cell metaplasia, and subepithelial fibrosis. Further, L-arginine increased ENO levels and cyclic guanosine monophosphate in lung and reduced the markers of nitro-oxidative stress such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. This was associated with reduced activity and expression of arginase 1, increased expression of endothelial NOS, and reduction of inducible NOS in bronchial epithelia.

Conclusion: We conclude that L-arginine administration may improve disordered nitric oxide metabolism associated with allergic airway inflammation, and alleviates some features of asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / drug effects
  • Arginase / metabolism
  • Arginine / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Asthma / pathology
  • Blotting, Western
  • Bronchial Hyperreactivity / drug therapy*
  • Bronchial Hyperreactivity / pathology
  • Disease Models, Animal
  • Eosinophilia / drug therapy
  • Immunohistochemistry
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / drug effects
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress / drug effects*

Substances

  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Arg1 protein, mouse
  • Arginase