Pharmacologically induced relaxation of tracheal smooth muscle is increased in hyperoxia-exposed 15-day-old rats

Hyperoxia increases maximum airway contractility in newborn guinea pigs and immature rats. Studies examining the mechanisms of hyperoxia-induced airway hyperresponsiveness have focused on contractile mechanisms, although excessive airway narrowing could be due to impaired relaxation. Our objective was to determine the effects of hyperoxia on airway structure and relaxing properties in juvenile rats exposed to an inspired fraction of oxygen (FiO2) of 0.5 within 24 hr of birth for 15 days, compared to a control group of air-exposed rats. We studied the 1) tracheal smooth muscle surface area; and 2) in vitro relaxation in precontracted (carbachol, 1.10−3 M) isolated tracheal rings to increasing cumulative concentrations (10−8 to 10−4 M) of salbutamol. There was no significant difference in the amount of smooth muscle between the hyperoxia and air-exposed groups. Maximal relaxation of the isolated trachea to salbutamol was greater in the hyperoxia group than in the air-exposed group when normalized to smooth muscle surface area (−12.69 ± 3.51 g/mm2 vs. − 8.49 ± 1.67 g/mm2; P (MANOVA) < 0.05) or expressed as maximal relaxation induced by 10−3 M theophylline (61% vs. 28%; P < 0.05). In conclusion, salbutamol-induced relaxation is enhanced (and not impaired) in newborn rats exposed to prolonged moderate hyperoxia. Pediatr Pulmonol. 2002; 33:124–129. © 2002 Wiley-Liss, Inc.