title: Indomethacin blocks airway tolerance to repetitive exercise but not to eucapnic hyperpnea in asthmatic subjects.
abstract: We have examined the effects of indomethacin (I) on tolerance to the bronchomotor effects of repetitive challenge with exercise (EX) and eucapnic hyperpnea (EH) in 7 asthmatic subjects. Each subject was studied on 4 separate days. EH was performed for 4 min at a minute ventilation found previously to increase specific airway resistance (SRaw) by 8 units (cm H2O/L/s). All exercise challenges were performed on a cycle ergometer for 5 min at a constant work load. Subjects breathed room temperature, dry air for both stimuli. SRaw was serially measured before and after each stimulus. Tolerance was examined by giving up to 3 repetitions of EH or EX, allowing a return of SRaw to within 1 unit of baseline between repetitions. Placebo (P) or I (25 mg four times a day for 7 doses) was administered in a single-blind manner. The timing between stimulus repetitions on the P day was matched to that of the I day. After P, the initial rise in SRaw was similar for both EX and EH, with a significant and progressive decrease in this rise after each stimulus repetition (p = 0.032 for EX, p = 0.006 for EH). After I, tolerance was still demonstrated to EH (p = 0.002), but not to EX (p = 0.231). This finding indicates that EH and EX are not identical stimuli, since there is an I-sensitive mechanism (possibly a bronchodilating prostaglandin) associated with the development of tolerance to EX but not to EH. Our data also suggest a possible additional bronchoconstricting mechanism associated with EX and not with EH.
authors: Cardiovascular Research Institute, University of California-San Francisco 94143-0130.
authors: D J
authors: DJ
authors: Margolskee
authors: B G
authors: BG
authors: Bigby
authors: H A
authors: HA
authors: Boushey
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000403:Airway Resistance; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006985:Hyperventilation / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D005082:Physical Exertion
chemical_list: D007213:Indomethacin