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

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 lipopolysaccharide (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. 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 wk of treadmill training, we assessed respiratory parameters, maximal oxygen consumption (V̇o2max), heart rate, systolic/diastolic/mean arterial pressures, skeletal muscle capillarization, and ex vivo vascular reactivity. At baseline, compared with Ctrl, ELA-LPS animals exhibited reduced V̇o2max, elevated blood pressure, and enhanced endothelium-dependent vasorelaxation via cyclooxygenase-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 nitric oxide (NO) signaling 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. Aerobic exercise training improved HR and BP in emphysema but failed to fully restore microvascular adaptations, suggesting disease-specific vascular remodeling. 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.NEW & NOTEWORTHY Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular comorbidities, but the vascular benefits of exercise remain uncertain. In an elastase-LPS rat model of COPD with preexisting vascular adaptations, aerobic training improves exercise capacity and lowers blood pressure but does not further enhance vascular reactivity or angiogenesis. Pathological vascular adaptations in COPD may interfere with the vascular benefits of aerobic training.