Abstract
We used a guinea-pig model of long-term exposure to cigarette-smoke to examine the antitussive effect of Bakumondoto (Mai-Men-Dong-Tang, TJ-29) on intractable coughs caused mainly by chronic smoking. The total number of coughs induced by capsaicin inhalation was significantly increased in guinea-pigs that had been exposed to mainstream cigarette smoke compared to that in naive guinea-pigs that had been exposed to fresh air. The antitussive effect of dihydrocodeine (10 mg/kg, p.o.) on the induced cough reflex was significantly attenuated in mainstream cigarette smoke-exposed guinea-pigs. On the other hand, the antitussive effect of TJ-29 (1 g/kg, p.o.) brought this level to the same as that in fresh air-exposed naive guinea-pigs. Nitric oxide (NO) metabolites in bronchoalveolar lavage fluid were markedly and significantly increased in mainstream cigarette smoke-exposed guinea-pigs compared to fresh air-exposed naive guinea-pigs. Furthermore, treatment with TJ-29 reduced these increased NO metabolites to the same levels as those in naive guinea-pigs that had been exposed to fresh air. These findings suggest that augmented NO release is associated with increased cough sensitivity as a result of mainstream cigarette smoke exposure. Furthermore, we can speculate that the antitussive effect of TJ-29 might be, at least in part, mediated by the inhibition of synthesis or release of NO.
