No abstract

Pulmonary arterial hypertension is associated with skeletal muscle myopathy and atrophy and impaired exercise tolerance. Aerobic exercise training has been recommended as a non-pharmacological therapy for deleterious effects imposed by pulmonary arterial hypertension. Aerobic physical training induces skeletal muscle adaptations via reduced inflammation, improved anabolic processes, decreased hypoxia and regulation of mitochondrial function. These benefits improve physical exertion tolerance and quality of life in patients with pulmonary arterial hypertension. However, the mechanisms underlying the therapeutic potential of aerobic exercise to skeletal muscle disfunctions in patients with pulmonary arterial hypertension are not well understood yet. This minireview highlights the pathways involved in skeletal muscle adaptations to aerobic exercise training in patients with pulmonary arterial hypertension.

The effects of voluntary running on the skeletal muscle of rats with pulmonary arterial hypertension (PAH) were tested in the present study. PAH was induced in rats by a single injection of monocrotaline (MCT, 60 mg/kg). Rats in the sedentary hypertension (HS) group had their tolerance to physical exertion reduced throughout the experiment, while those in the sedentary control (SC), exercise control (EC), exercise hypertension (EH) and median exercise (EM) groups maintained or increased. Despite that, the muscular citrate synthase activity was not different between groups. The survival time was higher in the EH (32 days) than in the SH (28 days) (p = 0.0032). SH and EH groups showed a lower percentage of muscle fiber and a higher percentage of extracellular matrix compared to control groups (p < 0.0001). However, the EM and EH groups presented higher percentage of muscle fiber and lower percentage of extracellular matrix than SH group (p < 0.0001). Regarding muscular gene expression, the SH and EM groups showed a lower expression of PGC1-α (p = 0.0024) and a higher expression of VEGF (p = 0.0033) compared to SC, while PGC1-α was elevated in the EH. No difference between groups was found for the carbonylated protein levels (p > 0.05), while the TNF-α/IL-10 ratio was augmented in the EH (p = 0.0277). In conclusion, voluntary running augments the proportion of fiber and affects the gene expression of inflammatory and mitochondrial biogenesis’ markers in the skeletal muscle of rats with MCT-induced PAH, which benefits their survival and tolerance to physical effort.