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 revel. 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-induced 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. Th us, direct in halation 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.