Mohammad Irshad Reza, Maxwell Mathias, Venkatachalem Sathish
University of Oklahoma Health Campus.
United States
American Journal of Physiology Lung Cullular and Molecular Physiology
Am J Physiol Lung Cell Mol Physiol 2026;
DOI: 10.1152/ajplung.00238.2026
Abstract
Chronic asthma can be associated with secondary pulmonary vascular dysfunction, however, the detailed functional profiling of the asthmatic pulmonary artery remains understudied. In this study, we characterized cardiopulmonary and vascular dysfunction in a chronic mixed allergen (MA) mouse model of asthma. Wild-type mice were intranasally challenged with MA or PBS for four weeks, followed by in vivo respiratory mechanics (flexiVent), ex vivo pulmonary artery wire myography, structural morphometry, and right ventricular analysis (Fulton Index). Chronic MA exposure induced significant airway hyperresponsiveness, evidenced by elevated airway resistance (Rrs) and elastance (Ers) with reduced compliance (Crs). Lung histology revealed increased pulmonary artery medial wall thickness and smooth muscle hyperplasia. Wire myography demonstrated enhanced serotonin (5-HT)-induced vasoconstriction and endothelial dysfunction in MA mice, evidenced by blunted endothelium-dependent relaxation to acetylcholine (ACh) with preserved endothelium-independent relaxation to sodium nitroprusside (SNP). Lastly MA mice had significant right ventricular hypertrophy by Fulton index. Collectively, chronic allergic airway inflammation drives vascular remodeling, endothelial dysfunction, and smooth muscle hyperreactivity in pulmonary arteries. This study demonstrates substantial structural and functional consequences of MA exposure to the pulmonary vasculature that models asthmatic pulmonary vascular dysfunction.
Category
Class I. Pulmonary Hypertension Associated with Inflammation
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes