Pulmo-protection of long-term swimming exercise via improving insulin sensitivity in monocrotaline-induced pulmonary hypertensive rats.

ABSTRACT

Exercise has been recognized as an effective intervention in the treatment of pulmonary arterial hypertension (PAH), supported by numerous studies. However, the precise effects of exercise on pulmonary function remain to be fully elucidated. In this study, using a rat model of swimming exercise training and monocrotaline-induced PAH, we aimed to explore its impact on pulmonary morphology and function. Our investigations revealed that MCT-treated rats exhibited augmented mean pulmonary arterial pressure (MPAP) and pulmonary vascular remodeling, which can be attenuated by 4 weeks of swimming exercise training (60 min/day, 5 days/week). Notably, MCT-treated rats showed impaired pulmonary function, as manifested by decreased tidal volume and dynamic compliance, which were reversed by exercise training. Assessment of pulmonary substrate in PAH rats indicated a prominent pro-inflammatory substrate, evidenced by macrophage accumulation through quantitative immunohistological analysis of macrophage-like cell expression (CD68), and extracellular matrix remodeling, evaluated by Masson staining. Importantly, both the pro-inflammatory substrate and extracellular matrix remodeling were ameliorated by swimming exercise training. Additionally, serum biochemical analysis demonstrated elevated levels of low-density lipoprotein cholesterol and Apolipoprotein B following MCT treatment, which were reduced with exercise intervention. Moreover, exercise enhanced systemic insulin sensitivity in both MCT-treated and untreated rats. Notably, MCT and exercise treatment both decreased fasting blood glucose (FBG) levels in rats, whereas exercise training reinstated FBG levels to normal in MCT-treated rats. In summary, our study suggests that swimming exercise confers a pulmonary protective effect in MCT-induced PAH rats, highlighting the potential importance of exercise-based rehabilitation in the management of PAH.