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Updated: Apr 23, 2026
Assessment of Respiratory Function in Conscious Mice by Double-chamber Plethysmography
Published on: July 10, 2018
The orl rat is more responsive to methacholine challenge than wild type
Elena Rodriguez1, Julia S Barthold2, Portia A Kreiger3
1Alfred I. duPont Hospital for Children, Nemours Lung Center, Wilmington, DE 19803, United States; Alfred I. duPont Hospital for Children, Nemours Biomedical Research, Wilmington, DE 19803, United States; Thomas Jefferson University, Division of Clinical Pharmacology, Dept. of Pharmacology and Experimental Therapeutics, Philadelphia, PA 19107, United States.
Rats with undescended testis (UDT) exhibit heightened airway hyperresponsiveness (AHR) to methacholine, a key asthma indicator. This UDT rat model shows promise for studying asthma mechanisms and testing new therapeutics.
Area of Science:
- Pulmonary Medicine
- Animal Models of Disease
- Asthma Pathophysiology
Background:
- Airway hyperresponsiveness (AHR) is a hallmark of asthma, involving exaggerated bronchoconstriction to stimuli.
- Undescended testis (UDT) is a common congenital anomaly in males, and a higher incidence of asthma symptoms is observed in boys with UDT.
- The orl rat, a substrain with inherited UDT, was investigated for its potential as a model for asthma-related AHR.
Purpose of the Study:
- To investigate the hypothesis that orl rats exhibit greater AHR compared to wild-type rats when challenged with methacholine.
- To establish and characterize a novel animal model for studying the link between cryptorchidism and asthma.
- To explore the role of specific inflammatory markers in the observed AHR.
Main Methods:
- Anesthetized Long Evans wild-type and orl rats (n=9 and n=13, respectively) underwent mechanical ventilation.
- Escalating concentrations of inhaled methacholine were administered to assess respiratory resistance, potency, and efficacy.
- Lung and diaphragm tissues were analyzed for interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α levels post-albuterol administration; histological analyses were also performed.
Main Results:
- orl rats demonstrated significantly increased sensitivity, hyperreactivity, and maximal response to methacholine, indicating greater AHR than wild-type rats.
- Histological examination revealed eosinophils in the lung tissue of orl rats, which were absent in wild-type rats.
- Interleukin-4 (IL-4) levels were upregulated in the diaphragm and downregulated in the lungs of orl rats following albuterol treatment.
Conclusions:
- orl rats exhibit significantly greater AHR to methacholine challenge compared to wild-type rats.
- Elevated IL-4 levels in diaphragmatic tissue homogenates were observed in orl rats, suggesting a potential role in UDT-associated AHR.
- This orl rat model provides a valuable preclinical tool for investigating the mechanistic links between cryptorchidism and asthma and for evaluating therapeutic interventions for AHR.
