Targeting Pulmonary Arterial Hypertension with Aerobic Training: Anti-Inflammatory and Cardioprotective Effects Enhance Survival in Experimental Models.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased right ventricular (RV) afterload, and high mortality. We investigated whether moderate aerobic training (AT) modulates inflammation, cardiopulmonary function, and survival in a monocrotaline (MCT)-induced PAH model. Male Wistar rats were randomized to non-trained (NT) or AT groups and treated with saline (SAL) or MCT: NT-SAL, NT-PAH, AT-SAL, AT-PAH. AT consisted of treadmill exercise at ~60% V̇O₂max, 5 days/week for 5 weeks, starting 3 weeks after PAH induction. Outcomes included cardiac function (echocardiography, PAT/PET), lung mechanics, histology (Movat pentachrome, diffuse alveolar damage, transmission electron microscopy), inflammatory biomarkers, and survival. Compared with NT-PAH, AT-PAH animals showed higher PAT/PET (P=0.003), smaller RV area (P=0.003), lower Fulton index (P=0.002), and reduced hepatic congestion (P=0.002). Lung elastance (P=0.006), parenchymal collagen (P=0.007), BALF total cells (P=0.04), and neutrophils (P<0.001) were lower in AT-PAH. Pulmonary arterioles exhibited higher IL-10 and lower IL-4, TNF-α, and VEGF (all P<0.001). Histology and ultrastructural analyses revealed reduced vascular remodeling, lower DAD scores, and preserved lung and myocardial architecture (all P<0.05). Survival was higher in AT-PAH (80% vs 60%, P=0.04). In conclusion, moderate AT before and after PAH induction improves RV-pulmonary artery coupling, reduces fibrosis and inflammation, preserves organ ultrastructure, and enhances survival. Integrating survival endpoints with noninvasive hemodynamics and dual-organ ultrastructural assessment provides mechanistic insight, supporting aerobic exercise as a potential non-pharmacological strategy in PAH. Further preclinical and clinical studies are needed to define optimal protocols and translational potential.