High-Intensity Exercise Training Alters the Effect of N -Acetylcysteine on Exercise-Related Muscle Ionic Shifts in Men.

This study investigated whether high-intensity exercise training alters the effect of -acetylcysteine (a precursor of antioxidant glutathione) on exercise-related muscle ionic shifts. We assigned 20 recreationally-active men to 6 weeks of high-intensity exercise training, comprising three weekly sessions of 4-10 × 20-s all-out bouts interspersed by 2 min recovery (SET, n = 10), or habitual lifestyle maintenance (n = 10). Before and after SET, we measured ionic shifts across the working muscle, using leg arteriovenous balance technique, during one-legged knee-extensor exercise to exhaustion with and without -acetylcysteine infusion. Furthermore, we sampled vastus lateralis muscle biopsies for analyses of metabolites, mitochondrial respiratory function, and proteins regulating ion transport and antioxidant defense. SET lowered exercise-related H, K, lactate, and Na shifts and enhanced exercise performance by ≈45%. While -acetylcysteine did not affect exercise-related ionic shifts before SET, it lowered H, HCO, and Na shifts after SET. SET enhanced muscle mitochondrial respiratory capacity and augmented the abundance of Na/K-ATPase subunits (α and β), ATP-sensitive K channel subunit (Kir6.2), and monocarboxylate transporter-1, as well as superoxide dismutase-2 and glutathione peroxidase-1. Collectively, these findings demonstrate that high-intensity exercise training not only induces multiple adaptations that enhance the ability to counter exercise-related ionic shifts but also potentiates the effect of -acetylcysteine on ionic shifts during exercise.