Airway hyperresponsiveness: From molecules to bedside - Selected contribution: Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats
Airway hyperresponsiveness: From molecules to bedside - Selected contribution: Hypersensitivity of pulmonary C fibers induced by adenosine in anesthetized rats
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DOI：
10.1152/japplphysiol.00107.2003
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发表时间：
2003-09-01
影响因子：
3.3
通讯作者：
Lee, LY
中科院分区：
文献类型：
--
作者：
Gu, QH;Ruan, T;Lee, LY
令人信服的临床证据表明腺苷在气道高反应性发展中的潜在作用，并表明肺感觉受体的参与。本研究旨在确定低剂量腺苷输注对麻醉开胸大鼠肺 C 纤维传入敏感性的影响。腺苷输注（40μg.kg(-1).min(-1)静脉注射，持续90秒）轻度升高肺C纤维的基线活性。然而，在腺苷输注期间，肺C纤维对化学兴奋剂的反应和肺膨胀（30 cmH(2)O气管压力）显着增强；例如，右心房注射辣椒素（0.25 或 0.5 杯/千克）的反应增加了五倍以上（对照和腺苷输注期间纤维活性的变化 = 2.64 +/- 0.67 和 16.27 +/- 3.11 脉冲/秒，n = 13，P < 0.05），并且这种增强的反应在 ∼ 10 分钟内恢复到控制。腺苷输注的增强作用被腺苷 A(1) 受体选择性拮抗剂 8-环戊基-1,3-二丙基黄嘌呤 (100 μg/kg) 预处理完全阻断，但不受 A(2) 受体拮抗剂 3,7-二甲基-1-炔丙基黄嘌呤 (1 mg/kg) 或3-乙基-5-苄基-2-甲基-4-苯基乙炔基-6-苯基-1,4-(+/-)-二氢吡啶-3,5-二羧酸酯 (2 mg/kg)，一种 A(3)-受体拮抗剂。这种增强作用也被腺苷 A(1) 受体的选择性激动剂 N-6-环戊基腺苷（0.25 μg . kg(-1) . min(-1) 持续 90 秒）模拟。总之，我们的结果表明，输注腺苷显着提高了大鼠肺部肺 C 纤维传入的敏感性，并且这种增强作用可能是通过激活腺苷 A(1) 受体介导的。
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 mug . 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(2)O tracheal pressure) were markedly potentiated; e.g., the response to right atrial injection ;of capsaicin (0.25 or 0.5 mug/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 A(1) 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 A(3)-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 A(1) 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 A(1) receptor.