In vivo exposure to hyperoxia increases airway responsiveness in rats. Demonstration in vivo and in vitro.
Studies regarding O2-induced lung injury have concentrated on damage to alveolar structures and pulmonary vasculature without consideration of alterations that may be occurring in airways. This study was undertaken to determine the effects of in vivo hyperoxic exposure on airway responses to excitatory stimuli in intact, anesthetized rats and in intrapulmonary bronchi isolated from hyperoxia-exposed rats. Using lung conductance (G1) as an index of bronchoconstriction, intravenously administered 5-hydroxytryptamine (5HT) elicited greater bronchoconstrictor responses in anesthetized, mechanically ventilated rats that had been exposed to 85% O2 for 7 days rather than to air. Further, airways of hyperoxia-exposed rats were more sensitive to the effects of intravenously administered 5HT as evidenced by the lower log dose of 5HT required to decrease G1 30%. Cylindrical segments of intrapulmonary bronchi isolated from hyperoxia-exposed rats were more responsive to the contractile effects of 5HT and electrical field stimulation. However, no differences in responsiveness to bethanechol or KCl were observed between the two groups. The log concentration of 5HT and the log frequency of electrical field stimulation that elicited half-maximal responses were smaller in bronchi isolated from hyperoxia-exposed animals, indicating an increase in sensitivity of the airways to these stimuli. These results suggest that prolonged exposure to greater than ambient levels of O2 can alter airway function; however, the mechanism responsible for these changes remains to be determined.
Szarek
J L
JL
Marshall University School of Medicine, Department of Pharmacology, Huntington, West Virginia 25755-9310.
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D010100:Oxygen / Q000502:physiology*; D011312:Pressure; D012123:Pulmonary Ventilation / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013990:Tidal Volume / Q000502:physiology
D012701:Serotonin; D010100:Oxygen