Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension

Abstract

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Inhibition of farnesyl pyrophosphate synthase improves pressure overload induced chronic cardiac remodeling

“…Upregulation of SERCA2a strengthened the cardiac contractility in acute cardiac dysfunction. In addition, an increased expression of SERCA2a could also be found in the early stage of metabolic syndrome23 and exercise24. However, the surplus energy demand created by SERCA2a may be harmful to the heart.…”

ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension

“…In PH rats, exercise training improved right ventricular function assessed by echocardiography (tricuspid annular plane maximal systolic velocity, tricuspid annular plane systolic excursion) and invasive haemodynamics (end-diastolic and end-systolic pressurevolume relationship) [91]. These functional changes were associated with an anti-inflammatory, antifibrotic and antiapoptotic effect [91]. In addition, a reduced oxidative stress and improved neurohumoral markers (lower N-terminal pro-brain natriuretic peptide (NT-proBNP) and endothelin-1 myocardial expression) were described in the right ventricle of trained PH animals.…”

“…The precise molecular impact of exercise training on right ventricular function remains unclear. In PH rats, exercise training improved right ventricular function assessed by echocardiography (tricuspid annular plane maximal systolic velocity, tricuspid annular plane systolic excursion) and invasive haemodynamics (end-diastolic and end-systolic pressurevolume relationship) [91]. These functional changes were associated with an anti-inflammatory, antifibrotic and antiapoptotic effect [91].…”

Exercise Training Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Stenosis

“…In a pulmonary hypertension model induced by monocrotaline, Colombo et al (2013) showed that hypertensive-exercised animals exhibited reduction in collagen, increase in vessels, and attenuation of diastolic dysfunction when compared with the hypertensive-untrained animals. A more recent study showed that exercise was capable of attenuating RV hypertrophy, improving cardiac function, and increasing exercise tolerance and survival in rats with pulmonary hypertension (Moreira-Gonçalves et al, 2015). Here, we have reported that exercise exerts several beneficial effects on RV remodeling induced by PAS.…”