Impact of exercise training on diaphragm and skeletal muscle blood flow in female pulmonary hypertensive rats

Introduction: Pulmonary hypertension (PH) is a disease characterized by vascular remodeling of the pulmonary arteries, increased respiratory muscle work, dyspnea, and exercise intolerance. Previous studies in our lab have found that diaphragm blood flow is increased in PH, due, in part, to chronic hyperventilation and impaired gas exchange. In this study we examined the effect of moderate intensity aerobic exercise on ameliorating these effects as they have been shown to increase exercise capacity and maximal blood flow to working skeletal muscle in healthy rats. We hypothesized that exercise trained PH (PH-EXT) rats would display greater [Formula: see text]O 2 peak compared to sedentary PH rats but less than healthy control (HC). We also hypothesized that total diaphragm blood flow during submaximal exercise and rest would be lower in PH-EXT rats compared to sedentary PH rats but greater than HC. Methods: Female Sprague-Dawley rats were randomized into 3 groups: HC (n=9), sedentary PH (PH-SED; n=11), and PH-EXT (n=11). All PH rats received a single dose of monocrotaline (MCT; 50 mg/kg, i.p.) whilst HC rats were administered saline. Disease progression was monitored regularly via echocardiography. All rats were acclimated to treadmill running for 5 days. Following acclimation PH-EXT rats performed 4 weeks of moderate intensity treadmill running (25m/min, 10% grade, increase of 5 min/day until 60 min was reached and maintained for training duration). Upon confirmation of PH (AT/ET< 0.30) a [Formula: see text]O 2 peak test was performed and rats were allowed ≥24 h to recover. Bulk skeletal muscle and diaphragm blood flow was determined via infusion of fluorescent microspheres at rest and during submaximal exercise (25 m/min, 10% grade). All results were analyzed via one-way ANOVA. Results: All PH rats displayed morphometric and echocardiographic criterion for disease including increased right ventricular systolic pressure (RVSP: avg.=39.5 mmHg), right ventricular (RV) hypertrophy (RV/LV+S: avg.=0.32), and reduced pulmonary artery acceleration time (PA AT/ET: avg.=0.26). PH-EXT [Formula: see text]O 2 peak was lower than HC (65 ± 2 ml/kg/min vs. 74 ± 3 ml/kg/min, P=0.031) but not different than PH-SED (68 ± 2 ml/kg/min, P=0.393). PH-EXT rats reached [Formula: see text]O 2 peak at greater speed than PH-SED (51 ± 1 m/min vs. 43 ± 2 m/min, P=0.003) but not different than HC (47 ± 2 m/min, P=0.083). PH-EXT rats also took longer to reach [Formula: see text]O 2 peak than both PH-SED (392 ± 15 s vs. 271 ± 20 s, P< 0.001) and HC (323 ± 20 s, P=0.027). There were no differences in regional diaphragm or hindlimb blood flow among all groups at rest or during exercise. Conclusion: These findings suggest that moderate continuous exercise training does not alter [Formula: see text]O 2 peak in PH, but promotes beneficial peripheral cardiovascular adaptations to exercise. The effect of exercise training on diaphragm and skeletal muscle blood flow will be determined as we as we expand this dataset. This study seeks to further elucidate the mechanisms in which exercise training may increase the quality of life within the PH population. This work was funded by the Sustained Momentum for Investigators with Laboratories Established (SMILE) Grant at Kansas State University College of Veterinary Medicine This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.