Resistance exercise training and blueberry extract protect against cardiac and skeletal muscle remodeling and metabolism disruptions in experimental pulmonary arterial hypertension

Abstract

Background: Pulmonary arterial hypertension (PAH) leads to heart failure, with limited treatment options to prevent adverse remodeling and metabolic dysfunctions. Exercise and bioactive compounds like blueberry extract show potential, but their combined effects are unclear. We tested if combining resistance exercise training (RT) and blueberry extract could protect against cardiac and skeletal muscle remodeling and metabolic disruptions in monocrotaline (MCT)-induced PAH. Methods: Male rats received MCT (60 mg/kg), blueberry extract (100 mg/kg/day), and RT (ladder climbing; 15 climbs at 55–65% max load, 5 times/week). Exercise tolerance, blood lactate levels, and echocardiography were assessed. After euthanasia, heart and biceps brachii were analyzed. RT and blueberry attenuated mortality, weight loss, and exercise intolerance in hypertensive rats. Results: Both interventions reduced pulmonary artery resistance and partially prevented right ventricular (RV) pressure overload and dysfunction, while their combination fully preserved left ventricular function. Hypertension-induced cardiac myocyte remodeling was mitigated by both interventions, with RT improving contractile function, whereas blueberry had no effect. Both treatments reduced oxidative stress and improved metabolic biomarkers in the RV. Blueberry preserved hypertrophy signaling pathways, while RT increased phospho (p)-Akt expression. Both interventions partially prevented reductions in p-mTOR, p-4E-BP1, and eIF4E, with their combination fully preserving these markers. Conclusions: RT program and blueberry extract employed, either alone or in combination, demonstrated protective effects against the progression of cardiac and skeletal muscle remodeling and metabolism disruptions in the MCT-induced PAH model.