The effect of rehabilitation exercise on the expression of glutaminase and cardiopulmonary remodeling in pulmonary hypertension

Pulmonary hypertension (PH) is featured by pulmonary vascular and cardiac remodeling. Rehabilitation exercise can improve patients’ quality of life. We previously pinpointed a potential glutamine metabolism dysfunction in PH. Hence, we aim to investigate whether rehabilitation exercise could mitigate right ventricular and pulmonary vascular remodeling and its effect on glutaminase (GLS). We collected clinical indicators of PH patients and analyzed their correlation with GLS. Rehabilitation exercise (moderate intensity swimming exercise) was performed in monocrotaline-induced PH (MCT-PH) rats. We found that plasma GLS1 level in patients was lower than healthy subjects, and it was negatively correlated with end-systolic stage eccentricity index, right atrial transverse dimension and right atrial longitudinal dimension. MCT-PH rats displayed pulmonary vascular remodeling and right ventricular hypertrophy. Compared to control rats, higher levels of GLS1 and GLS2 mRNA in lung and lower levels of these two isoforms of GLS in right ventricle (RV) were displayed in MCT-PH rats. After swimming exercise, GLS mRNA levels in the lung and RV were significantly upregulated, and the cross-sectional area of right ventricular cardiomyocytes was significantly decreased although the percentage of pulmonary arteriolar medial wall thickness was not significantly changed. Therefore, we hold the opinion that plasma GLS1 level was decreased in PH. The transcriptional levels of GLS1 and GLS2 were increased in the lung tissues in PH, but were decreased in the RV tissues. Meanwhile, the changes of GLS levels indicated the pulmonary vascular and right ventricular remodeling. Whereas moderate intensity swimming exercise might improve the right ventricular remodeling by regulating the levels of GLS.