NEDOCROMIL SODIUM REDUCES CIGARETTE SMOKE-INDUCED BRONCHOCONSTRICTOR HYPERRESPONSIVENESS TO SUBSTANCE-P IN THE GUINEA-PIG

Acute exposure to cigarette smoke provokes airway hyperresponsiveness to substance P and inactivates neutral endopeptidase (NEP). To determi ne whether nedocromil sodium can prevent cigarette smoke-induced hyper responsiveness to substance P, we studied two groups of anaesthetized guinea-pigs. One group of guinea-pigs was pretreated with aerosolized 0.9% NaCl solution (90 breaths), the other group was pretreated with a erosolized nedocromil sodium (10(-4) M, 90 breaths), In each animal, p retreatment was followed by either exposure to the smoke of one cigare tte or exposure to air, After acute exposure to cigarette smoke or to air, we measured the change in total pulmonary resistance (RL) induced by increasing concentrations of aerosolized substance P. In the absen ce of nedocromil sodium, the bronchoconstrictor responses to substance P were greater in cigarette smoke-exposed guinea-pigs than in air-exp osed animals, Aerosolized nedocromil sodium had no effect on the respo nse to substance P in air-exposed animals, but it reduced cigarette sm oke-induced hyperresponsiveness to substance P, The preventive effect on cigarette smoke-induced hyperresponsiveness to substance P was obse rved at concentrations of aerosolized nedocromil sodium of 3x10(-5), 1 0(-4), and 3x10(-4) M, In vitro, cigarette smoke solution inhibited NE P activity from lung membrane preparations, but this inhibitory effect was not modified by nedocromil sodium (10(-4) M). We conclude that ae rosolized nedocromil sodium reduces cigarette smoke-induced airway hyp erresponsiveness to substance P in vivo, This action of nedocromil sod ium is not due to a protective effect on cigarette smoke-induced inact ivation of NEP in vitro.