Cigarette smoke-induced airway oedema due to activation of capsaicin-sensitive vagal afferents and substance P release.
Exposure of rats to smoke from one cigarette caused local oedema due to a marked increased in vascular permeability from the epiglottis down to bronchioli, as indicated by extravasation of Evans blue in the airway mucosa. The cigarette smoke-induced extravasation of Evans blue was still present after removal of the tar and nicotine content of the smoke, suggesting that chemical irritants in the vapour phase were the main mediators of the vascular permeability response. Local or systemic pretreatment with capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11] SP, a substance P antagonist, abolished or significantly reduced the airway oedema induced by cigarette smoke or vagal nerve stimulation. No reduction of the cigarette smoke or vagally induced tracheal oedema was seen upon pretreatment with mepyramine plus cimetidine, fentanyl, disodiumchromoglycate, methylprednisolone or terbutaline. The results thus indicate that the cigarette smoke or vagally induced tracheal oedema is most likely to be due to substance P release from local capsaicin-sensitive afferent neurons in the airway mucosa. Local administration of substance P antagonists may be considered as a pharmacological means of inhibiting local mucosal oedema in the airways caused by airway irritants such as cigarette smoke.
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D004487:Edema / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000294:innervation; D012140:Respiratory Tract Diseases / Q000473:pathology*; D012907:Smoking; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects*
D013373:Substance P; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D002211:Capsaicin