Lin Ruei-Lung, Hayes Don, Lee Lu-Yuan
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
J Appl Physiol (1985). 2009 Jun;106(6):1917-24. doi: 10.1152/japplphysiol.00065.2009. Epub 2009 Mar 19.
A recent study by our laboratory has shown that an increase in intrathoracic temperature activates vagal pulmonary C-fibers. Because these afferents are known to elicit reflex bronchoconstriction upon stimulation, this study was carried out to investigate if an increase in airway temperature within the physiological range alters bronchomotor tone. Adult guinea pigs were anesthetized and mechanically ventilated via a tracheal tube. After the lung had been hyperventilated with humidified hot air (HHA) for 4 min, the tracheal temperature was elevated from 36.4 to 40.5 degrees C, which induced an immediate bronchoconstriction, increasing total pulmonary resistance (R(L)) to 177 +/- 10% and decreasing dynamic lung compliance to 81 +/- 6% of their respective baselines. The increase in R(L) returned spontaneously toward the baseline in <10 min and was reproducible in the same animals. There were no difference in the responses whether the humidity was generated from distilled water or isotonic saline. In contrast, hyperventilation with humidified air at room temperature did not cause any increase in R(L). The increase in R(L) caused by HHA was attenuated by 65.9% after a pretreatment with atropine alone and by 72.0% after a pretreatment with a combination of atropine and neurokinin receptor type 1 and 2 antagonists. In addition, capsazepine, a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, reduced the HHA-induced increase in R(L) by 64.1% but did not abolish it. However, pretreatment with formoterol, a beta(2)-agonist, completely prevented the HHA-induced bronchoconstriction. These results indicate that the increase in airway temperature induced transient airway constriction in guinea pigs. Approximately two-thirds of the increase in bronchomotor tone was mediated through the cholinergic reflex, which was probably elicited by the activation of TRPV1-expressing airway afferents. The remaining bronchoconstriction was caused by other, yet unidentified factors.
我们实验室最近的一项研究表明，胸腔内温度升高会激活迷走神经肺C纤维。由于已知这些传入神经在受到刺激时会引发反射性支气管收缩，因此开展本研究以调查生理范围内气道温度升高是否会改变支气管运动张力。成年豚鼠经麻醉后通过气管插管进行机械通气。在用湿化热空气（HHA）使肺过度通气4分钟后，气管温度从36.4℃升高至40.5℃，这立即诱发了支气管收缩，使总肺阻力（R(L)）增加至各自基线的177±10%，动态肺顺应性降低至各自基线的81±6%。R(L)的增加在不到10分钟内自发恢复至基线水平，且在同一动物中可重复出现。无论湿度是由蒸馏水还是等渗盐水产生，反应均无差异。相比之下，用室温湿化空气进行过度通气并未导致R(L)增加。单独用阿托品预处理后，HHA引起的R(L)增加减少了65.9%，用阿托品与1型和2型神经激肽受体拮抗剂联合预处理后减少了72.0%。此外，选择性瞬时受体电位香草酸亚型1（TRPV1）拮抗剂辣椒素使HHA诱导的R(L)增加减少了64.1%，但并未完全消除。然而，用β2受体激动剂福莫特罗预处理可完全防止HHA诱导的支气管收缩。这些结果表明，气道温度升高在豚鼠中诱发了短暂的气道收缩。支气管运动张力增加的约三分之二是通过胆碱能反射介导的，这可能是由表达TRPV1的气道传入神经激活引起的。其余的支气管收缩是由其他尚未明确的因素引起的。
