Genetic susceptibility to atracurium-induced bronchoconstriction.
The goal of this study was to develop a murine model of atracurium-induced bronchoconstriction in which to evaluate the mechanism of action of this airway response. We evaluated nine inbred strains of mice for the development of atracurium-induced bronchoconstriction. The maximal difference in the magnitude of the airway response to atracurium noted between the highly responsive DBA/2 mice and the minimally responsive SJL mice was greater than 20-fold. This phenotype appears to reflect an intrinsic difference in the lungs of these animals because the extent of neuromuscular blockade was not significantly different in DBA/2 and SJL mice. Atracurium-induced airway hyperresponsiveness in DBA/2 mice was eliminated in a dose-dependent manner by pretreatment with atropine or pancuronium. These data are consistent with a postganglionic vagal efferent mechanism which produces a differential pulmonary response to this neuromuscular blocker. A genetic predisposition to atracurium-induced bronchoconstriction appears to exist in certain inbred strains of mice. Thus, a mouse model may be useful for mapping the gene(s) that control this trait and for suggesting responsible candidate genes. Our results suggest that the inbred laboratory mouse will be useful to study the mechanism by which atracurium produces bronchoconstriction.
Levitt
R C
RC
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Ewart
S L
SL
D000818:Animals; D001279:Atracurium / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010197:Pancuronium / Q000494:pharmacology; D010641:Phenotype
D001279:Atracurium; D001285:Atropine; D010197:Pancuronium