EXPOSURE OF IMMATURE RATS TO HYPEROXIA INCREASES TRACHEAL SMOOTH-MUSCLE STRESS GENERATION IN-VITRO

Recently, we demonstrated that chronic exposure to hyperoxia causes in vivo airway muscarinic receptor hyperresponsiveness in the developing rat [Am. J. Physiol. 262 (Lung Cell. Mel. Physiol. 6): L263-L269, 199 2]. To test whether airway cholinergic hyperresponsiveness might resul t from intrinsic alterations in smooth muscle contractility, we measur ed the effect of in vivo hyperoxia on the contractile force elicited b y acetylcholine (ACh) of isometrically mounted tracheal rings in vitro . Tracheal rings were obtained from 3-wk-old rats exposed to air or to >95% O-2 for 8 days. Muscarinic responses were determined by measurin g the force elicited by exposure to increasing concentrations of ACh. Responses were normalized to the morphometrically determined tracheal smooth muscle cross-sectional area in a plane perpendicular to the axi s of force generation. In vivo O-2 exposure significantly increased ma ximal ACh induced stress generation (response to 10(-3) M ACh: air, 15 .92 +/- 1.37 g/mm(2) O-2, 21.78 +/- 1.52 g/mm(2); P = 0.010). The ACh induced stress generation of cylinders from hyperoxic rats was substan tially reduced by both epithelial removal and treatment with the cyclo oxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic e xposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the obser ved increase in maximal contractile responsiveness.