Adenosine-induced bronchoconstriction in human asthmatics: effects of pretreatment with indomethacin or atropine sulfate.
The present investigation was designed to evaluate the effects of pre-treatment with the cholinergic muscarinic receptor antagonist, atropine sulfate, or with the cyclooxygenase inhibitor, indomethacin, on adenosine-induced bronchoconstriction in human asthmatics. Eight male subjects with a FEV1 of greater than 70% of the predicted normal value underwent bronchial provocation challenges with adenosine and with the cholinergic agonist, methacholine, in a double-blind, randomized, cross-over fashion. The log10 of the agonist dose provoking a 20% decrease in FEV1 (log PD20FEV1) was used to assess airways responsiveness. Challenges were performed in the untreated state and 30 min after inhalation of atropine sulfate (0.05 mg/kg). Pre-challenge FEV1 values after atropine inhalation were higher than in the untreated state (p less than 0.01). Without atropine, the log PD20FEV1 values for adenosine were higher than those for methacholine (p less than 0.01). Atropine prevented a decrease in the FEV1 of 20% or more in seven of the eight subjects following inhalation of methacholine up to a concentration of 25 mg/ml, but did not significantly change the log PD20FEV1 for adenosine. The effects of a 75 mg oral dose of indomethacin or placebo, administered in a double-blind, randomized, cross-over fashion two hours before adenosine or methacholine challenge, were assessed in 12 asthmatics. In four subjects (two after placebo and two after indomethacin pretreatment), aerosols of the highest adenosine concentration (10 mg/ml) failed to decrease the FEV1 by 20% or more. In the remaining eight subjects, log PD20FEV1 values for adenosine or methacholine after indomethacin were not significantly different from those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Küng
M
M
Division of Pulmonary and Critical Care Medicine, University of Kentucky Medical Center, Lexington.
Diamond
L
L
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001285:Atropine / Q000494:pharmacology*; D001985:Bronchial Provocation Tests / Q000379:methods; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D001285:Atropine; D000241:Adenosine; D007213:Indomethacin