GENETIC SUSCEPTIBILITY TO ATRACURIUM-INDUCED BRONCHOCONSTRICTION

The goal of this study was to develop a murine model of atracurium-ind uced 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 note d between the highly responsive DBA/2 mice and the minimally responsiv e SJL mice was greater than 20-fold. This phenotype appears to reflect an intrinsic difference in the lungs of these animals because the ext ent 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 at ropine or pancuronium. These data are consistent with a postganglionic vagal efferent mechanism which produces a differential pulmonary resp onse to this neuromuscular blocker. A genetic predisposition to atracu rium-induced bronchoconstriction appears to exist in certain inbred st rains of mice. Thus, a mouse model may be useful for mapping the gene( s) that control this trait and for suggesting responsible candidate ge nes. Our results suggest that the inbred laboratory mouse will be usef ul to study the mechanism by which atracurium produces bronchoconstric tion.