BRONCHOCONSTRICTION AND DELAYED RAPID SHALLOW BREATHING INDUCED BY CIGARETTE-SMOKE INHALATION IN ANESTHETIZED RATS

Bronchomotor and ventilatory responses to inhalation of cigarette smoke (50% concentration, 6 ml) were studied in anesthetized and vagotomized Sprague-Dawley rats. Low-nicotine cigarette smoke did not cause any detectable delayed response, whereas high-nicotine cigarette smoke induced rapid, shallow breathing, and a marked increase in airway resistance (R(L)). The increase in f reached a peak (DELTA-f = 43 +/- 8%) at the 5th breath after the onset of smoke inhalation, preceding both the decrease in V(T) (DELTA-V(T) = -27 +/- 4%) and the increase in R(L) (DELTA-R(L) = 89 +/- 19%); the latter 2 reached their peaks at approximately the 10th breath, displaying a similar temporal pattern of responses between them. The bronchomotor response to high-nicotine cigarette smoke was slightly attenuated but not prevented by prior administration of isoproterenol (0.2 mg/kg, intravenously [iv]), nor was the smoke-induced rapid, shallow breathing. In contrast, prior administration of mecamylamine (0.9 mg/kg, iv) completely abolished both the bronchomotor and ventilatory responses to smoke inhalation, indicating that nicotine is the primary causative agent responsible for these changes.