Functional and Morphologic Dysfunctions on Airways of Rats Submitted to an Experimental Model of Obesity-exacerbated Asthma

Abstract

Obesity-exacerbated asthma phenotype is characterized by more severe asthma symptoms and glucocorticoid resistance. The aimed of this study is to standardize an obesity-exacerbated asthma model by high glycemic level index (HGLI) diet and ovalbumin (OVA) sensitization and challenges in Wistar rats. Animals were divided into groups: control (CG), obese (OG), asthmatic (AG), obese asthmatic (OAG) and obese asthmatic treated with dexamethasone (OADEXAG) and in vivo and in vitro functional and morphological parameters were measured. After HGLI consumption there was an increase in body weight, abdominal circumferences, body mass index, retroperitoneal, epididymal, inguinal adipose tissues and adiposity index. Respiratory function showed reduction in pulmonary tidal and minute-volume. In isolated trachea, the cumulative concentration-response curves for carbachol showed increase in contractile efficacy in OG, AG, OAG and OADEXAG, while OAG showed the greatest contractile efficacy. Histological sections of lungs showed an increased peribronchovascular inflammatory area on OAG, smooth muscle hypertrophy and remodeling area filled by extracellular matrix, and these changes were not reversed by treatment with dexamethasone. Obesity-exacerbated asthma model was successfully established. Therefore, this model allows further molecular investigations and the search for new therapeutic alternatives for the treatment and relief of symptoms of patients of obesity-induced resistant asthma.