Bronchoconstriction induced by hyperventilation with humidified hot air: role of TRPV1-expressing airway afferents.
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.
Lin
Ruei-Lung
RL
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Hayes
Don
D
Lee
Lu-Yuan
LY
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006358:Hot Temperature; D006813:Humidity; D006979:Hyperthermia, Induced / Q000379:methods*; D006985:Hyperventilation / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D013047:Specific Pathogen-Free Organisms; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
D001549:Benzamides; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D010880:Piperidines; D018039:Receptors, Tachykinin; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; C073839:SR 48968; D001285:Atropine; D014364:Tryptophan; D002211:Capsaicin; D000068759:Formoterol Fumarate