Am. J. Respir. Crit. Care Med., Vol 151, No. 6, Jun 1995, 1752-1762.
Mechanisms and modulation of airway plasma exudation after direct inhalation of cigarette smoke
YH Lei, PJ Barnes and DF Rogers
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
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.
