Complex interplay between disease and aerobic exercise training on vascular function in an exacerbated emphysema rat model

Aim: Chronic obstructive pulmonary disease (COPD) is a respiratory disease with systemic complications including vascular dysfunction. Aerobic exercise improves blood pressure, endothelial function, and muscle angiogenesis in health and disease, but these effects in COPD are inconsistent. The elastase and LPS-induced emphysema (ELA-LPS) model with exacerbation replicates COPD cardiovascular comorbidities. We aimed to assess the impact of aerobic exercise on blood pressure and endothelial determinants in this model. Methods: Male Wistar rats were assigned to four groups: controls (Ctrl), controls with exercise (Ctrl+Ex), emphysema (ELA-LPS), and emphysema with exercise (ELA-LPS+Ex). After 4 weeks of treadmill training, we assessed respiratory parameters, V̇O₂max, heart rate, systolic/diastolic/mean arterial pressures, skeletal muscle capillarization, and ex vivo vascular reactivity. Results: At baseline, compared to Ctrl, ELA-LPS animals exhibited reduced V̇O₂max, elevated blood pressure, and enhanced endothelium-dependent vasorelaxation via COX-dependent pathways. Aerobic exercise increased exercise capacity, lowered heart rate (HR), and reduced blood pressure (BP) in both groups. In Ctrl+Ex, aerobic exercise enhanced endothelium-dependent relaxation through NO signalling and increased muscle capillarization. In contrast, in ELA-LPS+Ex, aerobic exercise did not further increased vasorelaxation, although NO-dependence of the endothelium-dependent relaxation was restored, and no increase in muscle capillarization was observed. Conclusion: Aerobic exercise training improved HR and BP in emphysema but failed to fully restore microvascular adaptations, suggesting disease-specific vascular remodelling. These findings highlight a complex interplay between training-induced and disease-induced vascular changes. Clinical studies are warranted to define vascular phenotypes of patients with COPD responsive to aerobic exercise-induced blood pressure reduction.