The Potential of Alamandine in Airway Hyperresponsiveness in an Ovalbumin-Induced Asthma Model

Background: Asthma is a chronic inflammatory airway disease characterized by variable airflow obstruction and tissue remodeling. Alamandine (ALA), a renin-angiotensin system (RAS) peptide with anti-inflammatory properties, remains poorly explored in allergic respiratory disease. Objectives: This study evaluated prophylactic (33 days) and therapeutic (21 days) subcutaneous ALA (50 µg/kg/day) administration in an ovalbumin (OVA)-induced rat asthma model. Methods: Twenty male Wistar rats were assigned to four groups: control (CO), OVA with prophylactic ALA (ALA-P; days 1-33), OVA with therapeutic ALA (ALA-T; days 12-33), and OVA-only control (OVA). Rats were sensitized (days 1-3) and challenged with aerosolized OVA (days 6-33). On day 34, ventilatory mechanics were assessed via FlexiVent, including methacholine challenge (12.5 mg/mL). Pulmonary inflammation was evaluated by eosinophil quantification; MrgD/Mas and AT1 receptor expression by immunohistochemistry and Western blot, respectively. Results: OVA animals exhibited elevated baseline airway resistance and bronchoconstriction, and eosinophil infiltration. ALA-T significantly attenuated the respiratory symptoms, restoring airway resistance and eosinophil infiltration to CO-group levels, whereas ALA-P exhibited only a partial reduction. MrgD and Mas expression were elevated in OVA, reflecting compensatory RAS activation, but normalized in both ALA-treated groups. No significant differences in AT1 expression were observed. Conclusions: ALA likely exerts bronchoprotective and anti-allergic effects in this model via MrgD/Mas modulation. The ALA-MrgD/Mas axis represents a potential therapeutic target for allergic airway diseases, particularly when conventional treatments are insufficient.