TY - JOUR
T1 - Airway hyperresponsiveness
T2 - From molecules to bedside - Selected contribution: Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats
AU - Gu, Qihai
AU - Ruan, Ting
AU - Hong, Ju Lun
AU - Burki, Nausherwan
AU - Lee, Lu Yuan
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
KW - Adenosine receptor
KW - Airway hyperresponsiveness
KW - Chemical irritants
KW - Dyspnea
KW - Lung afferents
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U2 - 10.1152/japplphysiol.00107.2003
DO - 10.1152/japplphysiol.00107.2003
M3 - Article
C2 - 12754169
AN - SCOPUS:0042423422
SN - 8750-7587
VL - 95
SP - 1315
EP - 1324
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 3
ER -