Methacholine-induced bronchoconstriction and airway smooth muscle in the guinea pig

We examined the role of airway smooth muscle (ASM) as a determinant of the site and extent of methacholine (MCh)-induced airway narrowing in anesthetized and mechanically ventilated guinea pigs. The sites of airway narrowing and ASM were determined in animals (n = 4) bronchoconstricted to 75, 60, 40, or 15% of the maximal lung resistance (RL,max) induced by aerosolized MCh and compared with a saline-challenged animal. The median luminal area of each animal was significantly inversely correlated to the percentage of RL,max (r = -0.95; P < 0.01). However, there was no correlation between the degree of narrowing of any given airway and the quantity of ASM of any given airway. The relationship between the amount of ASM and responsiveness to MCh was studied in different animals (n = 13). The range of the concentration of MCh required to reach 50% of RL,max (EC50) varied by 254-fold, but the RL,max had only a 3.6-fold range. There was no correlation between RL,max and ASM. However, there was a correlation between the log EC50 and ASM (r = -0.541; P<0.05) in intraparenchymal cartilaginous airways. In conclusion, morphometric measurements of airway narrowing are correlated with pulmonary resistance. Variability in the quantity of ASM does not appear to be a determinant of the heterogeneity of airway narrowing or of maximal bronchoconstriction among normal guinea pigs. However, the sensitivity to MCh is associated with differences in the amount of ASM in intraparenchymal cartilaginous airways.