Ruan Ting, Lin You Shuei, Lin Kae-Shin, Kou Yu Ru
Dept. of Physiology, School of Medicine, National Yang-Ming Univ., Shih-Pai, Taipei 112, Taiwan.
J Appl Physiol (1985). 2006 Aug;101(2):644-54. doi: 10.1152/japplphysiol.00192.2006. Epub 2006 Apr 20.
Inhalation of H2O2 is known to evoke bradypnea followed by tachypnea, which are reflexes resulting from stimulation by reactive oxygen species of vagal lung capsaicin-sensitive and myelinated afferents, respectively. This study investigated the pharmacological receptors and chemical mediators involved in triggering these responses. The ventilatory responses to 0.2% aerosolized H2O2 were studied before and after various pharmacological pretreatments in anesthetized rats. The initial bradypneic response was reduced by a transient receptor potential vanilloid 1 (TRPV1) receptor antagonist [capsazepine; change (Delta) = -53%] or a P2X purinoceptor antagonist [iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (PPADS); Delta = -47%] and was further reduced by capsazepine and iso-PPADS in combination (Delta = -78%). The initial bradypneic response was reduced by a cyclooxygenase inhibitor (indomethacin; Delta = -48%), ATP scavengers (apyrase and adenosine deaminase in combination; Delta = -50%), or capsazepine and indomethacin in combination (Delta = -47%), was further reduced by iso-PPADS and indomethacin in combination (Delta = -75%) or capsazepine and ATP scavengers in combination (Delta = -83%), but was not affected by a lipoxygenase inhibitor (nordihydroguaiaretic acid) or by any of the various vehicles. No pretreatment influenced delayed tachypnea. We concluded that 1) the initial bradypneic response to H2O2 results from activation of both TRPV1 and P2X receptors, possibly located at terminals of vagal lung capsaicin-sensitive afferent fibers; 2) the functioning of the TRPV1 and P2X receptors in triggering the initial bradypnea is, in part, mediated through the actions of cyclooxygenase metabolites and ATP, respectively; and 3) these mechanisms do not contribute to the H2O2-evoked delayed tachypnea.
已知吸入过氧化氢会引发呼吸减慢，随后出现呼吸急促，这两种反应分别是由活性氧刺激迷走神经肺辣椒素敏感和有髓传入神经所引起的反射。本研究调查了引发这些反应所涉及的药理受体和化学介质。在麻醉大鼠中，研究了在各种药理预处理前后对0.2%雾化过氧化氢的通气反应。初始呼吸减慢反应可被瞬时受体电位香草酸受体1（TRPV1）拮抗剂[辣椒素；变化（Δ）=-53%]或P2X嘌呤受体拮抗剂[异吡哆醛-6-偶氮苯-2',5'-二磺酸盐（PPADS）；Δ=-47%]降低，且辣椒素和异PPADS联合使用时进一步降低（Δ=-78%）。初始呼吸减慢反应可被环氧化酶抑制剂（吲哚美辛；Δ=-48%）、ATP清除剂（联合使用腺苷三磷酸双磷酸酶和腺苷脱氨酶；Δ=-50%）或辣椒素和吲哚美辛联合使用（Δ=-47%）降低，异PPADS和吲哚美辛联合使用（Δ=-75%）或辣椒素和ATP清除剂联合使用（Δ=-83%）时进一步降低，但不受脂氧合酶抑制剂（去甲二氢愈创木酸）或任何不同载体的影响。没有预处理影响延迟性呼吸急促。我们得出结论：1）对过氧化氢的初始呼吸减慢反应是由TRPV1和P2X受体的激活引起的，这些受体可能位于迷走神经肺辣椒素敏感传入纤维的终末；2）TRPV1和P2X受体在引发初始呼吸减慢中的作用分别部分通过环氧化酶代谢产物和ATP的作用介导；3）这些机制与过氧化氢诱发的延迟性呼吸急促无关。
