Tracheal responsiveness to both isoprenaline and beta2‐adrenoreceptor blockade by propranolol in cigarette smoke exposed and sensitized guinea pigs

Abstract

Airway hyperresponsiveness is the main feature of asthma and also exists in cigarette smokers. In previous studies we have shown increased airway responsiveness to isoprenaline in asthmatic patients and smokers. In this study, tracheal responsiveness to isoprenaline and beta-adrenergic receptor blockade was investigated in animals exposed to cigarette smoke (AECS) with or without sensitization by ovalbumin (OA). Guinea pigs were exposed to cigarette smoke over a 3-month period with or without sensitization by injection and inhalation of OA. Tracheal responses in AECS, AECS + sensitized and control animals (n = 7 for each group) to isoprenaline in the absence and presence of 20 nmol/L propranolol were measured and EC(50) was established. The propranolol blockade (concentration ratio minus one (CR-1)) was calculated (post-propranolol EC(50)/EC(50)) - 1. The tracheal response of AECS and AECS + sensitized guinea pigs to isoprenaline was significantly higher than that of control animals (EC(50): 4.24 +/- 0.54, 3.66 +/- 0.53 and 7.71 +/- 0.68.79 micromol for AECS, AECS + sensitized and control animals, respectively) (P < 0.001). There was no significant difference in EC(50) between AECS and AECS + sensitized. CR-1 was also significantly higher in the trachea of AECS and AECS + sensitized compared with controls (13.39 +/- 2.22 and 15.35 +/- 2.95 vs. 3.10 +/- 0.6, P < 0.05 in both cases). There was no significant difference in CR-1 between AECS and AECS + sensitized. There was a significant correlation between the tracheal response to isoprenaline (EC(50)) and CR-1 (r =-0.731, P < 0.001). There was no significant difference in tracheal maximum response to isoprenaline between the three groups of animals. The results of this study indicate an increased tracheal response to a beta(2)-adrenergic stimulating drug and enhanced beta(2)-adrenergic blockade by propranolol in both AECS and AECS + sensitized. These results suggest similar increase in airway responsiveness to beta(2)-adrenergic agonists and beta(2)-receptor blockade in AECS and AECS + sensitized guinea pigs.