Mechanisms and modulation of airway plasma exudation after direct inhalation of cigarette smoke.
We characterized plasma exudation induced by direct inhalation of cigarette smoke in anesthetized, artificially ventilated guinea pigs, using Evans blue dye as a plasma marker, and investigated the neurogenic mechanisms underlying the response. Cigarette smoke increased plasma exudation in the lower trachea, main bronchi, and proximal intrapulmonary airways in a dose-related manner. Exudation was rapid in onset and was maintained for 0.5 to 2 h, depending upon airway level. Exudation was not reduced after removal of the particular phase of the smoke, nor by atropine, phentolamine, propranolol, hexamethonium, antihistamines, or bilateral vagotomy. Nicotine, at a dose calculated to approximate that in the plasma of cigarette-exposed animals, did not increase airway plasma exudation. Cigarette smoke-induce exudation was blocked by capaicinization or by a substance P antagonist and was potentiated by phosphoramidon but not by captopril. Nedocromil sodium or morphine (0.1 mg/kg each intravenously) partially inhibited cigarette smoke-induced exudation but had no effect on the response to substance P. Inhibition by morphine, but not that by nedocromil sodium, was reversed by naloxone. Thus, direct inhalation of cigarette smoke induces a dose-related, long-lasting increase in airway plasma exudation that is due to vapor-phase activation of sensory-efferent nerves, release of sensory neuropeptides that mediate the exudative response via interaction with substance P receptors, and regulation by neutral endopeptidase. The inhibitory effect of nedocromil and morphine on cigarette smoke-induced airway plasma exudation occurs through inhibition of neurotransmission.
Lei
Y H
YH
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Barnes
P J
PJ
Rogers
D F
DF
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010947:Plants, Toxic; D012906:Smoke / Q000009:adverse effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014026:Nicotiana; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*
D012906:Smoke; D009538:Nicotine