Airway hyperresponsiveness: From molecules to bedside - Selected contribution: Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats

Qihai Gu, Ting Ruan, Ju Lun Hong, Nausherwan Burki, Lu Yuan Lee

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Compelling clinical evidence implicates the potential role of adenosine in development of airway hyperresponsiveness and suggests involvement of pulmonary sensory receptors. This study was carried out to determine the effect of a low dose of adenosine infusion on sensitivity of pulmonary C-fiber afferents in anesthetized open-chest rats. Infusion of adenosine (40 μg·kg -1·min-1 iv for 90 s) mildly elevated baseline activity of pulmonary C fibers. However, during adenosine infusion, pulmonary C-fiber responses to chemical stimulants and lung inflation (30 cmH 2O tracheal pressure) were markedly potentiated; e.g., the response to right atrial injection of capsaicin (0.25 or 0.5 μg/kg) was increased by more than fivefold (change in fiber activity = 2.64 ± 0.67 and 16.27 ± 3.11 impulses/s at control and during adenosine infusion, n = 13, P < 0.05), and this enhanced response returned to control in ∼10 min. The potentiating effect of adenosine infusion was completely blocked by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (100 μg/kg), a selective antagonist of the adenosine A1 receptor, but was not affected by 3,7-dimethyl-1-propargylxanthine (1 mg/kg), an A 2-receptor antagonist, or 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(±) -dihydropyridine-3,5-dicarboxylate (2 mg/kg), an A3-receptor antagonist. This potentiating effect was also mimicked by N 6-cyclopentyladenosine (0.25 μg·kg -1·min-1 for 90 s), a selective agonist of the adenosine A1 receptor. In conclusion, our results showed that infusion of adenosine significantly elevated the sensitivity of pulmonary C-fiber afferents in rat lungs and that this potentiating effect is likely mediated through activation of the adenosine A1 receptor.

Original languageEnglish
Pages (from-to)1315-1324
Number of pages10
JournalJournal of Applied Physiology
Volume95
Issue number3
DOIs
StatePublished - Sep 1 2003

Keywords

  • Adenosine receptor
  • Airway hyperresponsiveness
  • Chemical irritants
  • Dyspnea
  • Lung afferents

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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