Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea-pigs

Clin Exp Allergy. 1997 Oct;27(10):1219-26.

Abstract

Background: Administration of propranolol can provoke bronchoconstriction only in asthmatic patients. Recently we developed an animal model for propranolol-induced bronchoconstriction (PIB). Our working hypothesis is that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction.

Objectives: Our goal in this study was to determine which products of arachidonate 5-lipoxygenase pathway are involved in the PIB.

Methods: Propranolol at a concentration of 10 mg/mL was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea-pigs. Two different sulfidopeptide leukotriene (s-LT) antagonists, ICI198 615 in the doses of 0.03 and 0.3 mg/kg and vehicle and KCA757 in the doses of 1 and 5 mg/kg and vehicle, and a LTB4 antagonist ONO4057 in the doses of 1 and 10 mg/kg and vehicle were injected intravenously 15 min after antigen challenge. Effects of an anticholinergic agent atropine sulphate (5mg/kg) and an alpha-adrenergic blocker phentolamine (0.3 and 3 mg/kg) were examined in the same way.

Results: Bronchoconstriction occurred when 10 mg/mL of propranolol was inhaled 20 min after antigen challenge. Both ICI198 615 and KCA757 administered intravenously 15 min after antigen challenge reduced the PIB in a dose-dependent manner while ONO4057 did not alter the PIB. Atropine or phentolamine did not change the PIB.

Conclusions: These results suggest that mediator mechanism, but not cholinergic or alpha-adrenergic nerve, is important in the PIB which developed after the allergic bronchoconstriction in our guinea-pig model and that s-LTs but not LTB4 have an important role in the pathophysiology of the PIB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Atropine / pharmacology
  • Bronchial Provocation Tests
  • Bronchoconstriction / drug effects
  • Bronchoconstriction / immunology*
  • Guinea Pigs
  • Hypersensitivity, Immediate / drug therapy
  • Hypersensitivity, Immediate / immunology*
  • Leukotriene Antagonists
  • Leukotrienes / immunology*
  • Male
  • Muscarinic Antagonists / pharmacology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Ovalbumin / immunology
  • Phentolamine / pharmacology
  • Propranolol / immunology*

Substances

  • Adrenergic alpha-Antagonists
  • Leukotriene Antagonists
  • Leukotrienes
  • Muscarinic Antagonists
  • Atropine
  • Ovalbumin
  • Propranolol
  • Phentolamine