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. Mol. Physiol. 6): L263-L269, 1992]. To test whether airway cholinergic hyperresponsiveness might result from intrinsic alterations in smooth muscle contractility, we measured the effect of in vivo hyperoxia on the contractile force elicited by acetylcholine (ACh) of isometrically mounted tracheal rings in vitro. Tracheal rings were obtained from 3-wk-old rats exposed to air or to > 95% O2 for 8 days. Muscarinic responses were determined by measuring 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 axis of force generation. In vivo O2 exposure significantly increased maximal ACh-induced stress generation (response to 10(-3) M ACh: air, 15.92 +/- 1.37 g/mm2; O2, 21.78 +/- 1.52 g/mm2; P = 0.010). The ACh-induced stress generation of cylinders from hyperoxic rats was substantially reduced by both epithelial removal and treatment with the cyclooxygenase inhibitor indomethacin. We conclude that in vivo hyperoxic exposure increases tracheal smooth muscle contractile function in vitro and that epithelium-derived prostaglandin(s) contributes to the observed increase in maximal contractile responsiveness.
Hershenson
M B
MB
Department of Pediatrics, University of Chicago, Illinois 60637-1470.
Wylam
M E
ME
Punjabi
N
N
Umans
J G
JG
Schumacker
P T
PT
Mitchell
R W
RW
Solway
J
J
D000818:Animals; D000831:Animals, Newborn; D046508:Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D009092:Mucous Membrane / Q000502:physiology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012130:Respiratory Hypersensitivity / Q000209:etiology*; D013314:Stress, Mechanical; D014132:Trachea / Q000503:physiopathology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010100:Oxygen