Oxygen radicals in bronchoconstriction of guinea pigs elicited by isocapnic hyperpnea.
The role of oxygen radicals in isocapnic hyperpnea-induced bronchoconstriction (HIB) of guinea pigs was investigated using scavengers of the radicals. In series 1, 50 young guinea pigs were randomly divided into seven groups: control 1, control 2, chlorisondamine, tetrodotoxin (TTX), acute dimethylthiourea (DMTU), tachykinin depletion, and 5% CO2 in air. Animals of the control 2 group received vehicle (saline) infusion while those of the control 1 group did not. Chlorisondamine was used to block ganglionic transmission, TTX to interrupt nerve conduction, DMTU to scavenge hydroxyl radicals, and chronic capsaicin pretreatment to deplete tachykinins. The animals in the last group were ventilated with dry 5% CO2 in air during hyperpnea. In series 2, 13 additional animals were used to test the effects of intratracheal administration of superoxide dismutase and catalase (SOD + CAT) on HIB. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and mechanically ventilated. During the baseline period, each animal was ventilated normally with humidified air. Then it was hyperventilated 15 min with a dry gas mixture of 95% O2-5% CO2, except animals in the last group of series 1. Subsequently, all animals returned to normal ventilation with humidified air for 45 min (recovery period). The maximal expiratory flow and dynamic compliance were obtained periodically during the recovery period. The isocapnic hyperpnea using 95% O2-5% CO2, but not 5% CO2 in air, caused bronchoconstriction that was significantly blocked by acute DMTU, acute SOD + CAT, and tachykinin depletion. In an additional group of six animals, acute DMTU did not significantly alter acetylcholine-induced airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Fang
Z X
ZX
Pharmacology and Experimental Therapeutics Division, College of Pharmacy, University of Kentucky, Lexington 40536.
Lai
Y L
YL
D000818:Animals; D001369:Axons / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002245:Carbon Dioxide / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D016166:Free Radical Scavengers; D005609:Free Radicals; D006168:Guinea Pigs; D008170:Lung Compliance / Q000502:physiology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D016166:Free Radical Scavengers; D005609:Free Radicals; D015320:Tachykinins; D002245:Carbon Dioxide; D013779:Tetrodotoxin; D002374:Catalase; D013482:Superoxide Dismutase