Strain-related differences in airway smooth muscle and airway responsiveness in the rat.

The purpose of this study was to evaluate the possible role of the quantity of airway smooth muscle (AWSM) as a determinant of differences in responsiveness between inbred rat strains. To do this, we studied several batches of 8- to 10-wk-old Lewis and Fisher 344 rats. Animals were anesthetized intraperitoneally with pentobarbital (30 mg/kg) and xylazine (7 mg/kg). The peak value of pulmonary resistance (RL) was measured after progressively doubling concentrations of inhaled aerosolized methacholine (MCh). The MCh concentration required to double RL (EC200RL) was calculated as an index of airway responsiveness. Fisher rats were significantly more responsive than Lewis, and the interstrain variability in responsiveness was significantly greater than the intrastrain variability. Additional animals from the less responsive Lewis strain (n = 8) and the more responsive F344 strain (n = 11) were killed immediately after measurement of responsiveness, and AWSM was quantitated as a fraction of total lung tissue using a point-counting technique. F344 rats were again significantly more responsive than Lewis rats (EC200RL geometric mean: 0.72 versus 2.16 mg/ml, p less than 0.005). F344 rats also had significantly more AWSM than did Lewis rats (3.22 +/- 0.176 versus 2.48 +/- 0.185%, mean +/- SE, p less than 0.001). We conclude that highly inbred Fisher rat strains characteristically exhibit a degree of airways responsiveness greater than that of the Lewis strain and that the quantity of AWSM may be an important determinant of interstrain differences.

Partitioning of airway responses to inhaled methacholine in the rat.

We measured the changes in upper and lower airway resistance after inhalation of aerosols of methacholine (MCh) in doubling concentrations (16, 32, 64, and 128 mg/ml) in 11 anesthetized nonintubated spontaneously breathing rats. Upper airway resistance (Ru) increased from a control value of 0.48 +/- 0.04 cmH2O X ml-1 X s (mean +/- SE) to 0.85 +/- 0.15 after 128 mg/ml MCh, whereas lower airway resistance (Rlo) increased from 0.11 +/- 0.03 to 0.21 +/- 0.04. However, there was no correlation between the magnitudes of the changes in Ru and Rlo. In a further seven anesthetized spontaneously breathing rats aerosols of MCh were delivered into the lower airways via a tracheostomy and resulted in increases in Rlo from a control value of 0.20 +/- 0.03 to 0.66 +/- 0.12 after 128 mg/ml MCh. Ru also increased to approximately double its control value. We conclude that inhaled MCh causes narrowing of both Ru and Rlo in the anesthetized rat, the changes in Ru and Rlo are not correlated, and changes in Ru can occur when MCh deposition occurs only in the lower airways.