Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats

Abstract

Pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) is an experimental protocol of right heart failure. We analyzed the role of exercise training on the right ventricle structure and function, pulmonary artery remodeling, and GSK-3β expression. Rats were divided among the following groups: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM). Rats underwent exercise training for a period of 5 weeks, with 3 weeks post-MCT injection. Rats in the SM and TM groups presented with an increase in right ventricle hypertrophy indexes and lung congestion. The right ventricular end diastolic pressure (RVEDP), right ventricular systolic pressure (RVSP), and its minimum and maximal pressure derivates were increased in the SM and TM groups. The right ventricle interstitial volume pulmonary artery thickness and p-GSK-3β/GSK-3β were increased in the MCT groups as compared with the control groups. The TM group had a reduction in interstitial volume, p-GSK-3β/GSK-3β ratio, pulmonary artery thickness, RVEDP, and an increase in intramyocardial vessels volume as compared with the SM group. The overall results have shown that the exercise protocol used promoted positive changes in right ventricle and pulmonary artery remodeling. These observations also suggest that structural remodeling may be influenced by signaling proteins, such as GSK-3β.

Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline

“…This increase in pulmonary pressure seems to be insufficient to induce RV hypertrophy, as was demonstrated in this study, which corroborates previous data from our laboratory (Siqueira et al 2011). This outcome differed from that observed in male rats, where an evident RV hypertrophy was documented (Colombo et al 2013). These findings agree with reports showing that female rats develop less PAH in response to MCT than males (Bal et al 2013).…”

Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension

“…Studies in animal models of pulmonary hypertension have shown that exercise training is associated with improvement in endothelium-dependent relaxation in the pulmonary circulation, favorable remodeling of pulmonary vasculature, and reduced right ventricle enddiastolic pressure. 45,46 Furthermore, recent human studies have shown that exercise training is associated with significant improvements in central pulmonary perfusion and peripheral skeletal muscle function, which could also contribute to the training-related improvement in exercise capacity. 16,23 In this study, we observed a significant improvement in the pulmonary arterial systolic pressure with training, which could lead to significant reductions in pulmonary vascular resistance and a concomitant improvement in blood flow through the pulmonary vascular system.…”

Principles of Rehabilitation and Reactivation: Pulmonary Hypertension

“…Furthermore, in the same study, exercise training was associated with reductions in pulmonary artery diameters (-46%, p < 0.05), interstitial volume (-60%, p < 0.05) and right ventricular end-diastolic pressure (-45%, p < 0.05) [16]. The authors found a 37% reduction (p < 0.05) in the ratio between the phosphorylated (inactive/prohypertrophic) and the dephosphorylated (active/antihypertrophic) form of glycogen synthase kinase [16]. These results led the authors to speculate that glycogen synthase kinase signaling is probably involved in the positive effects of exercise training in PH.…”

“…Another animal model with Wistar rats using the same exercise protocol revealed significant improvement in capillary density (+86%, p < 0.05), up to near-normal values [16]. Furthermore, in the same study, exercise training was associated with reductions in pulmonary artery diameters (-46%, p < 0.05), interstitial volume (-60%, p < 0.05) and right ventricular end-diastolic pressure (-45%, p < 0.05) [16].…”