The incidence of respiratory diseases is constantly increasing. Although asthma-related mortality has improved over the years, mortality risk remains high. This is primarily due to non-respiratory causes such as cardiovascular diseases. Reduced lung function has been associated with elevated cardiovascular risk. Here we investigated the relationship between vascular and airway function focusing on the role of cyclooxygenase (COX)-derived mediators. C57BL/6, endothelial-COX-1 knockout (EC-COX1 KO), fibroblast-COX-1 knockout (Fsp-COX-1 KO), and ovalbumin (OVA)-sensitized BALB/c mice have been used. Functional studies showed the key role of COX-1-derived mediators in maintaining the bronchial tone in C57BL/6 mice. Selective inhibition of bronchial COX-1 increased the reactivity of airways. The same effect was observed by targeting vascular COX. Bronchi from EC-COX1 KO, but not from Fsp-COX-1 KO, displayed an increased airway reactivity. This relationship was also evident following allergen exposure. OVA sensitization caused both bronchial and vascular remodeling. Further, OVA exposure enhanced the expression of adhesion molecules in bronchi and vessels resulting in peribronchial as well as perivascular eosinophilia. Finally, vascular lectin up-regulation following OVA exposure confirmed the immunological interaction between vessel district and airways. In conclusion, we evidenced a functional interaction between bronchi and vessels both in physiological and pathological conditions such as asthma.