Cycling with blood flow restriction improves performance and muscle K+ regulation and alters the effect of anti-oxidant infusion in humans.

KEY POINTS: Training with blood flow restriction (BFR) is a well-recognized strategy for promoting muscle hypertrophy and strength. However, its potential to enhance muscle function during sustained, intense exercise remains largely unexplored. In the present study, we report that interval training with BFR augments improvements in performance and reduces net K+ release from contracting muscles during high-intensity exercise in active men. A better K+ regulation after BFR-training is associated with an elevated blood flow to exercising muscles and altered muscle anti-oxidant function, as indicated by a higher reduced to oxidized glutathione (GSH:GSSG) ratio, compared to control, as well as an increased thigh net K+ release during intense exercise with concomitant anti-oxidant infusion. Training with BFR also invoked fibre type-specific adaptations in the abundance of Na+ ,K+ -ATPase isoforms (α1 , ß1 , phospholemman/FXYD1). Thus, BFR-training enhances performance and K+ regulation during intense exercise, which may be a result of adaptations in anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level. ABSTRACT: We examined whether blood flow restriction (BFR) augments training-induced improvements in K+ regulation and performance during intense exercise in men, and also whether these adaptations are associated with an altered muscle anti-oxidant function, blood flow and/or with fibre type-dependent changes in Na+ ,K+ -ATPase-isoform abundance. Ten recreationally-active men (25 ± 4 years, 49.7 ± 5.3 mL kg-1  min-1 ) performed 6 weeks of interval cycling, where one leg trained without BFR (control; CON-leg) and the other trained with BFR (BFR-leg, pressure: ∼180 mmHg). Before and after training, femoral arterial and venous K+ concentrations and artery blood flow were measured during single-leg knee-extensor exercise at 25% (Ex1) and 90% of thigh incremental peak power (Ex2) with i.v. infusion of N-acetylcysteine (NAC) or placebo (saline) and a resting muscle biopsy was collected. After training, performance increased more in BFR-leg (23%) than in CON-leg (12%, P < 0.05), whereas K+ release during Ex2 was attenuated only from BFR-leg (P < 0.05). The muscle GSH:GSSG ratio at rest and blood flow during exercise was higher in BFR-leg than in CON-leg after training (P < 0.05). After training, NAC increased resting muscle GSH concentration and thigh net K+ release during Ex2 only in BFR-leg (P < 0.05), whereas the abundance of Na+ ,K+ -ATPase-isoform α1 in type II (51%), ß1 in type I (33%), and FXYD1 in type I (108%) and type II (60%) fibres was higher in BFR-leg than in CON-leg (P < 0.05). Thus, training with BFR elicited greater improvements in performance and reduced thigh K+ release during intense exercise, which were associated with adaptations in muscle anti-oxidant function, blood flow and Na+ ,K+ -ATPase-isoform abundance at the fibre-type level.

Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects.

KEY POINTS: Mechanotransduction in endothelial cells is a central mechanism in the regulation of vascular tone and vascular remodelling Mechanotransduction and vascular function may be affected by high sugar levels in plasma because of a resulting increase in oxidative stress and increased levels of advanced glycation end-products (AGE). In healthy young subjects, 2 weeks of daily supplementation with 3 × 75 g of sucrose was found to reduce blood flow in response to passive lower leg movement and in response to 12 W of knee extensor exercise. This vascular impairment was paralleled by up-regulation of platelet endothelial cell adhesion molecule (PECAM)-1, endothelial nitric oxide synthase, NADPH oxidase and Rho family GTPase Rac1 protein expression, an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. There were no measurable changes in AGE levels. The findings of the present study demonstrate that daily high sucrose intake markedly affects mechanotransduction proteins and has a detrimental effect on vascular function. ABSTRACT: Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day-1 for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2%) and to 12 W of active exercise (by 9 ± 1%), indicating impaired vascular function. A reduced flow response to passive and active exercise was paralleled by a significant up-regulation of platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho family GTPase Rac1 protein expression in the muscle tissue, as well as an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. The phosphorylation status was not acutely altered with passive leg movement. These findings indicate that a regular intake of high levels of sucrose can impair vascular mechanotransduction and increase the oxidative stress potential, and suggest that dietary excessive sugar intake may contribute to the development of vascular disease.