MORPHOMETRIC CHANGES DURING THE EARLY AIRWAY RESPONSE TO ALLERGEN CHALLENGE IN THE RAT

The purpose of this study was to determine the relative contributions of airway wall edema and smooth muscle contraction to the early response (ER) of allergic bronchoconstriction. Brown Norway rats, 6 to 7 wk old, were sensitized with ovalbumin (OA). Anesthetized rats were challenged with either OA or saline 2 wk later. Pulmonary resistance (RL) was measured every minute until either it increased to 150% of the baseline, defined as a significant ER, or until 15 min elapsed. Eight OA-challenged test rats with a significant ER and eight saline-challenged control rats were used for morphometric studies. The lungs were quick-frozen with liquid nitrogen, processed with freeze substitution, and sagittal sections (5 mum) were stained with hematoxylin and eosin. The airway lumen subtended by the epithelial basement membrane (LuB) and cross sectional airway wall area (AW) of all airways were measured by camera lucida and digitization. The LuB and AW of each airway was standardized for size by dividing by the ideal airway lumen (LuB(ideal)), which was calculated from the length of basement membrane, assuming a perfect circle in the unconstricted state. The cumulative frequency distribution of the LuB/LuB(ideal) for the airways from test rats was shifted to the left compared with the control rats (p < 0.01), indicating airway narrowing after challenge. Airway narrowing increased as a function of airway size. Cumulative frequency distributions of AW/LuB(ideal) showed that there was a significant increase in the wall thickness of only the small airways of test animals. We conclude that in the Brown Norway rat, the ER to inhalational challenge with OA is mainly caused by smooth muscle contraction rather than airway wall edema.