Airway and inflammatory profile of ORL rats: An asthma phenotype?

Introduction: The ORL rat is a Long Evans substrain with inherited cryptorchidism. We have observed respiratory distress and wheezing in a subset of this strain but no respiratory phenotype is available. Objective: We hypothesized that ORL rats would exhibit airway responsiveness (AR) associated with inflammation. To address this question, we investigated whether respiratory mechanics and biomarkers of inflammation in these rats would be different at baseline (BL) or during methacholine (MCh) challenge induced constriction. Material and methods: Long Evans WT (n=9) and ORL (n=14) rats were anesthetized, tracheostomized, placed in a plethysmograph (Buxco, Rodent RC Site), mechanically ventilated and challenged with 0.3 to 12.5 mg/ml of aerosolized MCh. We calculated resistance (R) and compliance (C), and lung tissue homogenates were assayed for IL-4, IL-6, and TNF-α using ELISA; quantitative histomorphometry is ongoing. We performed 2-way ANOVA of physiological outcomes and inflammatory markers. Results: Respiratory challenges with MCh increased R and decreased C as a function of dose and group (WT vs. ORL), ORL rats had increased (p= Conclusions: ORL rats compared with WT rats were significantly more responsive to MCh challenges, indicated large and small airway reactivity and exhibited decreased expression of IL-6 and IL-4 in lung tissue. The observed respiratory reactivity in this strain of ORL rats may provide a genetic animal model for the study of asthma and associated genetic/hormonal/environmental factors.