Th. Hsu et al., SMOKE-INDUCED AIRWAY HYPERRESPONSIVENESS TO INHALED WOOD SMOKE IN GUINEA-PIGS - TACHYKININERGIC AND CHOLINERGIC MECHANISMS, Life sciences (1973), 63(17), 1998, pp. 1513-1524
Citations number
40
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
The smoke-induced airway hyperresponsiveness (SIAHR) to inhaled wood s
moke was investigated in anesthetized guinea pigs. Two smoke challenge
s teach 10 mi) separated by 30 min were delivered into the lungs by a
respirator. In control animals, SIAHR was evidenced by an average bron
choconstrictive response tan increase in total lung resistance) to the
second smoke challenge (SM2) that was similar to 4.3-fold greater tha
n that to the first challenge (SM1). Pretreatment with CP-96,345 and S
R-48,968 (neurokinin-l and -2 receptor antagonists; each 1 mg/kg) in c
ombination totally prevented this SIAHR, while pretreatment with CP-96
,344 and SR-48,965 (inactive enantiomers of CP-96,345 and SR-48,968, e
ach 1 mg/kg) in combination failed to do so. Pretreatment with CP-96,3
45 (1 mg/kg), SR-48,968 (1 mg/kg), or atropine (50 mu g/kg) significan
tly alleviated this SIAHR. Pretreatment with phosphoramidon [an inhibi
tor of neutral endopeptidase (NEP); 2 mg/kg], which suppresses the deg
radation of tachykinins, induced an increase in airway reactivity that
largely mimicked this SIAHR. The NEP activity measured in airway tiss
ues excised 30 min after SM1 was significantly lower than that in air
control value. These results suggest that 1) a prior wood smoke exposu
re induces an airway hyperresponsiveness to the subsequent wood smoke
inhalation, 2) a tachykininergic mechanism involving both neurokinin-l
and -2 receptors is essential for, and a cholinergic mechanism is als
o involved in the development of this SIAHR, and 3) inactivation of ai
rway NEP by wood smoke may contribute to this SIAHR.